The Experts below are selected from a list of 891 Experts worldwide ranked by ideXlab platform
Andreas Stengel - One of the best experts on this subject based on the ideXlab platform.
-
NUCB2 nesfatin 1 inhibitory effects on food intake body weight and metabolism
Peptides, 2020Co-Authors: Martha A. Schalla, Masatomo Mori, Yvette Tache, Suraj Unniappan, Nils Lambrecht, Andreas StengelAbstract:Since its discovery in 2006 by Oh-I and colleagues, NUCB2/nesfatin-1 encoded by nucleobindin-2 (NUCB2) has drawn sustained attention as reflected in over 500 publications. Among those, more than half focused on the alterations of food intake, body weight and metabolism (glucose, fat) induced by nesfatin-1 and/or NUCB2/nesfatin-1. In the current review we discuss the existing literature focusing on NUCB2/nesfatin-1's influence on food intake, body weight and glucose as well as fat metabolism and highlight gaps in knowledge.
-
NUCB2/nesfatin-1 - Inhibitory effects on food intake, body weight and metabolism.
Peptides, 2020Co-Authors: Martha A. Schalla, Masatomo Mori, Yvette Tache, Suraj Unniappan, Nils Lambrecht, Andreas StengelAbstract:Since its discovery in 2006 by Oh-I and colleagues, NUCB2/nesfatin-1 encoded by nucleobindin-2 (NUCB2) has drawn sustained attention as reflected in over 500 publications. Among those, more than half focused on the alterations of food intake, body weight and metabolism (glucose, fat) induced by nesfatin-1 and/or NUCB2/nesfatin-1. In the current review we discuss the existing literature focusing on NUCB2/nesfatin-1's influence on food intake, body weight and glucose as well as fat metabolism and highlight gaps in knowledge.
-
Role of Brain NUCB2/nesfatin-1 in the Stress-induced Modulation of Gastrointestinal Functions.
Current neuropharmacology, 2016Co-Authors: Miriam Goebel-stengel, Andreas StengelAbstract:BACKGROUND Nucleobindin2 (NUCB2)/nesfatin-1 plays a well-established role in homeostatic functions associated with food intake and stress integration. AIM This review focusses on NUCB2/nesfatin-1's central effects on gastrointestinal functions and will summarize the effects on food intake, motility and secretion with focus on the upper gastrointestinal tract. RESULTS We will highlight the stressors that influence brain NUCB2/nesfatin-1 expression and discuss functional implications. In addition to traditional acute psychological and physical stressors such as restraint stress and abdominal surgery we will look at immunological, visceral and metabolic stressors as well as a chronic combination stress model that have been shown to affect NUCB2/nesfatin-1 signaling and describe associated functional consequences.
-
role of brain NUCB2 nesfatin 1 in the stress induced modulation of gastrointestinal functions
Current Neuropharmacology, 2016Co-Authors: Miriam Goebelstengel, Andreas StengelAbstract:BACKGROUND Nucleobindin2 (NUCB2)/nesfatin-1 plays a well-established role in homeostatic functions associated with food intake and stress integration. AIM This review focusses on NUCB2/nesfatin-1's central effects on gastrointestinal functions and will summarize the effects on food intake, motility and secretion with focus on the upper gastrointestinal tract. RESULTS We will highlight the stressors that influence brain NUCB2/nesfatin-1 expression and discuss functional implications. In addition to traditional acute psychological and physical stressors such as restraint stress and abdominal surgery we will look at immunological, visceral and metabolic stressors as well as a chronic combination stress model that have been shown to affect NUCB2/nesfatin-1 signaling and describe associated functional consequences.
-
sex specific regulation of NUCB2 nesfatin 1 differential implication in anxiety in obese men and women
Psychoneuroendocrinology, 2015Co-Authors: Tobias Hofmann, Ulf Elbelt, Anne Ahnis, Matthias Rose, Burghard F. Klapp, Andreas StengelAbstract:Abstract Nesfatin-1 is cleaved from nucleobindin2 (NUCB2) and implicated in the regulation of hunger and satiety as anorexigenic peptide hormone. Circulating NUCB2/nesfatin-1 is elevated in obesity and decreased in anorexia nervosa. In addition, a role in the regulation of stress, anxiety and depression has been demonstrated. First evidence suggested that NUCB2/nesfatin-1 might be regulated in a sex-specific manner. Thus, we investigated NUCB2/nesfatin-1 plasma levels in association with perceived stress, anxiety and depressiveness in obese men and women. We enrolled 140 inpatients (87 female, 53 male; body mass index, BMI, 30.3–81.7 kg/m 2 ) hospitalized due to obesity with mental and somatic comorbidities. Perceived stress (PSQ-20), anxiety (GAD-7), and depressiveness (PHQ-9) were measured psychometrically, and at the same time NUCB2/nesfatin-1 plasma levels by ELISA. Males and females did not differ in terms of age and BMI. NUCB2/nesfatin-1 did not show a correlation with age or BMI. Mean NUCB2/nesfatin-1 levels (+25%, p p p p = 0.02) were higher in females compared to males. Scores for perceived stress ( r = 0.39; p r = 0.35; p p > 0.19). The strongest association was observed between NUCB2/nesfatin-1 and anxiety with a positive correlation in women ( r = 0.54; p r = −0.32; p = 0.03). This result was reflected in higher NUCB2/nesfatin-1 levels in women with high versus low anxiety (+51%, p p = 0.04) after a median split into two groups with high and low anxiety. In conclusion, circulating NUCB2/nesfatin-1 showed a positive correlation with anxiety, perceived stress, and depressiveness in obese women. In men, no correlation with perceived stress and depressiveness was observed, whereas the association with anxiety was inverse, pointing towards a sex-specific regulation. These results corroborate the suggestion of NUCB2/nesfatin-1 being relevantly involved in the regulation of mood and stress in a sex-specific way.
Toshihiko Yada - One of the best experts on this subject based on the ideXlab platform.
-
Islet β-cell-produced NUCB2/nesfatin-1 maintains insulin secretion and glycemia along with suppressing UCP-2 in β-cells
The Journal of Physiological Sciences, 2019Co-Authors: Yifei Yang, Masanori Nakata, Masatomo Mori, Boyang Zhang, Jun Nakae, Toshihiko YadaAbstract:Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia.
-
islet β cell produced NUCB2 nesfatin 1 maintains insulin secretion and glycemia along with suppressing ucp 2 in β cells
Journal of Physiological Sciences, 2019Co-Authors: Masanori Nakata, Toshihiko Yada, Masatomo Mori, Yifei Yang, Boyang Zhang, Jun NakaeAbstract:Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia.
-
Paraventricular NUCB2/Nesfatin-1 Supports Oxytocin and Vasopressin Neurons to Control Feeding Behavior and Fluid Balance in Male Mice
Endocrinology, 2016Co-Authors: Masanori Nakata, Masatomo Mori, Boyang Zhang, Takashi Okada, Darambazar Gantulga, Putra Santoso, Chiaki Masuda, Toshihiko YadaAbstract:Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.
-
paraventricular NUCB2 nesfatin 1 supports oxytocin and vasopressin neurons to control feeding behavior and fluid balance in male mice
Endocrinology, 2016Co-Authors: Masanori Nakata, Masatomo Mori, Boyang Zhang, Takashi Okada, Darambazar Gantulga, Putra Santoso, Chiaki Masuda, Toshihiko YadaAbstract:Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.
-
paraventricular NUCB2 nesfatin 1 is directly targeted by leptin and mediates its anorexigenic effect
Biochemical and Biophysical Research Communications, 2015Co-Authors: Gantulga Darambazar, Masanori Nakata, Masatomo Mori, Takashi Okada, Lei Wang, Atsumi Shinozaki, Megumi Motoshima, Toshihiko YadaAbstract:Abstract An adipokine leptin plays a central role in the regulation of feeding and energy homeostasis via acting on the hypothalamus. However, its downstream neuronal mechanism is not thoroughly understood. The neurons expressing nucleobindin-2 (NUCB2)-derived nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) have been implicated in feeding and energy homeostasis. The present study aimed to explore the role of PVN NUCB2/nesfatin-1 in the leptin action, by using adeno-associated virus (AAV) vectors encoding shRNA targeting NUCB2 (AAV-NUCB2-shRNA). Leptin directly interacted and increased cytosolic Ca 2+ in single neurons isolated from the PVN, predominantly in NUCB2/nesftin-1-immunoreactive neurons. Treatment with leptin in vivo and in vitro markedly increased NUCB2 mRNA expression in the PVN. Peripheral and central injections of leptin failed to significantly inhibit food intake in mice receiving AAV-NUCB2. These results indicate that PVN NUCB2/nesfatin-1 is directly targeted by leptin, and mediates its anorexigenic effect.
Defang Chen - One of the best experts on this subject based on the ideXlab platform.
-
The inhibitory effect of NUCB2/nesfatin-1 on appetite regulation of Siberian sturgeon (Acipenser baerii Brandt).
Hormones and Behavior, 2018Co-Authors: Xin Zhang, Yuanbing Wu, Jinwen Qi, Zhengzhi Tian, Shuyao Wang, Ni Tang, Hu Chen, Bin Wang, Defang ChenAbstract:Abstract Since NUCB2 was discovered, the information about NUCB2/nesfatin-1 in appetite regulation in both mammals and teleost has been still limited. The present study aims to determine the effects of nesfatin-1 on food intake and to explore the appetite mechanism in Siberian sturgeon. In this study, NUCB2 cDNA sequence of 1571 bp was obtained, and the mRNA expression of NUCB2 was abundant in brain and liver. Levels of NUCB2 were appreciably increased in brain after feeding 1 and 3 h, while significantly decreased within fasting 15 days. Except for fasting 1 day, the expression pattern of NUCB2 in the liver was similar to the brain. Acute intraperitoneal (i.p.) injection of nesfatin-1 inhibited the food intake during 0–1 h in a dose-dependent manner and 50 or 100 ng/g BW nesfatin-1 significantly decreased the cumulative food intake during 3 h. The daily food intake and cumulative food intake were remarkably reduced post chronic (7 days) i.p. injection. Moreover, chronic i.p. injection of nesfatin-1 affected the expression of appetite factors including cart, apelin and pyy in the brain, stomach and liver with the consistent pattern of change, while the levels of cck, ucn3 and NUCB2 in these have different patterns. This study demonstrates that nesfatin-1 acts as a satiety factor in reducing the short-term and long-term food intake of Siberian sturgeon. Therefore, the data suggesting nesfatin-1 inhibits the appetite through different signal pathways in the central and peripheral endocrine systems of Siberian sturgeon.
-
The inhibitory effect of NUCB2/nesfatin-1 on appetite regulation of Siberian sturgeon (Acipenser baerii Brandt).
Hormones and Behavior, 2018Co-Authors: Xin Zhang, Yuanbing Wu, Jinwen Qi, Zhengzhi Tian, Shuyao Wang, Ni Tang, Hu Chen, Bin Wang, Defang ChenAbstract:Abstract Since NUCB2 was discovered, the information about NUCB2/nesfatin-1 in appetite regulation in both mammals and teleost has been still limited. The present study aims to determine the effects of nesfatin-1 on food intake and to explore the appetite mechanism in Siberian sturgeon. In this study, NUCB2 cDNA sequence of 1571 bp was obtained, and the mRNA expression of NUCB2 was abundant in brain and liver. Levels of NUCB2 were appreciably increased in brain after feeding 1 and 3 h, while significantly decreased within fasting 15 days. Except for fasting 1 day, the expression pattern of NUCB2 in the liver was similar to the brain. Acute intraperitoneal (i.p.) injection of nesfatin-1 inhibited the food intake during 0–1 h in a dose-dependent manner and 50 or 100 ng/g BW nesfatin-1 significantly decreased the cumulative food intake during 3 h. The daily food intake and cumulative food intake were remarkably reduced post chronic (7 days) i.p. injection. Moreover, chronic i.p. injection of nesfatin-1 affected the expression of appetite factors including cart, apelin and pyy in the brain, stomach and liver with the consistent pattern of change, while the levels of cck, ucn3 and NUCB2 in these have different patterns. This study demonstrates that nesfatin-1 acts as a satiety factor in reducing the short-term and long-term food intake of Siberian sturgeon. Therefore, the data suggesting nesfatin-1 inhibits the appetite through different signal pathways in the central and peripheral endocrine systems of Siberian sturgeon.
-
the inhibitory effect of NUCB2 nesfatin 1 on appetite regulation of siberian sturgeon acipenser baerii brandt
Hormones and Behavior, 2018Co-Authors: Xin Zhang, Zhengzhi Tian, Shuyao Wang, Ni Tang, Hu Chen, Bin Wang, Jin Hao, Defang ChenAbstract:Abstract Since NUCB2 was discovered, the information about NUCB2/nesfatin-1 in appetite regulation in both mammals and teleost has been still limited. The present study aims to determine the effects of nesfatin-1 on food intake and to explore the appetite mechanism in Siberian sturgeon. In this study, NUCB2 cDNA sequence of 1571 bp was obtained, and the mRNA expression of NUCB2 was abundant in brain and liver. Levels of NUCB2 were appreciably increased in brain after feeding 1 and 3 h, while significantly decreased within fasting 15 days. Except for fasting 1 day, the expression pattern of NUCB2 in the liver was similar to the brain. Acute intraperitoneal (i.p.) injection of nesfatin-1 inhibited the food intake during 0–1 h in a dose-dependent manner and 50 or 100 ng/g BW nesfatin-1 significantly decreased the cumulative food intake during 3 h. The daily food intake and cumulative food intake were remarkably reduced post chronic (7 days) i.p. injection. Moreover, chronic i.p. injection of nesfatin-1 affected the expression of appetite factors including cart, apelin and pyy in the brain, stomach and liver with the consistent pattern of change, while the levels of cck, ucn3 and NUCB2 in these have different patterns. This study demonstrates that nesfatin-1 acts as a satiety factor in reducing the short-term and long-term food intake of Siberian sturgeon. Therefore, the data suggesting nesfatin-1 inhibits the appetite through different signal pathways in the central and peripheral endocrine systems of Siberian sturgeon.
Masatomo Mori - One of the best experts on this subject based on the ideXlab platform.
-
NUCB2 nesfatin 1 inhibitory effects on food intake body weight and metabolism
Peptides, 2020Co-Authors: Martha A. Schalla, Masatomo Mori, Yvette Tache, Suraj Unniappan, Nils Lambrecht, Andreas StengelAbstract:Since its discovery in 2006 by Oh-I and colleagues, NUCB2/nesfatin-1 encoded by nucleobindin-2 (NUCB2) has drawn sustained attention as reflected in over 500 publications. Among those, more than half focused on the alterations of food intake, body weight and metabolism (glucose, fat) induced by nesfatin-1 and/or NUCB2/nesfatin-1. In the current review we discuss the existing literature focusing on NUCB2/nesfatin-1's influence on food intake, body weight and glucose as well as fat metabolism and highlight gaps in knowledge.
-
NUCB2/nesfatin-1 - Inhibitory effects on food intake, body weight and metabolism.
Peptides, 2020Co-Authors: Martha A. Schalla, Masatomo Mori, Yvette Tache, Suraj Unniappan, Nils Lambrecht, Andreas StengelAbstract:Since its discovery in 2006 by Oh-I and colleagues, NUCB2/nesfatin-1 encoded by nucleobindin-2 (NUCB2) has drawn sustained attention as reflected in over 500 publications. Among those, more than half focused on the alterations of food intake, body weight and metabolism (glucose, fat) induced by nesfatin-1 and/or NUCB2/nesfatin-1. In the current review we discuss the existing literature focusing on NUCB2/nesfatin-1's influence on food intake, body weight and glucose as well as fat metabolism and highlight gaps in knowledge.
-
Islet β-cell-produced NUCB2/nesfatin-1 maintains insulin secretion and glycemia along with suppressing UCP-2 in β-cells
The Journal of Physiological Sciences, 2019Co-Authors: Yifei Yang, Masanori Nakata, Masatomo Mori, Boyang Zhang, Jun Nakae, Toshihiko YadaAbstract:Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia.
-
islet β cell produced NUCB2 nesfatin 1 maintains insulin secretion and glycemia along with suppressing ucp 2 in β cells
Journal of Physiological Sciences, 2019Co-Authors: Masanori Nakata, Toshihiko Yada, Masatomo Mori, Yifei Yang, Boyang Zhang, Jun NakaeAbstract:Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia.
-
Paraventricular NUCB2/Nesfatin-1 Supports Oxytocin and Vasopressin Neurons to Control Feeding Behavior and Fluid Balance in Male Mice
Endocrinology, 2016Co-Authors: Masanori Nakata, Masatomo Mori, Boyang Zhang, Takashi Okada, Darambazar Gantulga, Putra Santoso, Chiaki Masuda, Toshihiko YadaAbstract:Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.
Masanori Nakata - One of the best experts on this subject based on the ideXlab platform.
-
Islet β-cell-produced NUCB2/nesfatin-1 maintains insulin secretion and glycemia along with suppressing UCP-2 in β-cells
The Journal of Physiological Sciences, 2019Co-Authors: Yifei Yang, Masanori Nakata, Masatomo Mori, Boyang Zhang, Jun Nakae, Toshihiko YadaAbstract:Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia.
-
islet β cell produced NUCB2 nesfatin 1 maintains insulin secretion and glycemia along with suppressing ucp 2 in β cells
Journal of Physiological Sciences, 2019Co-Authors: Masanori Nakata, Toshihiko Yada, Masatomo Mori, Yifei Yang, Boyang Zhang, Jun NakaeAbstract:Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia.
-
Paraventricular NUCB2/Nesfatin-1 Supports Oxytocin and Vasopressin Neurons to Control Feeding Behavior and Fluid Balance in Male Mice
Endocrinology, 2016Co-Authors: Masanori Nakata, Masatomo Mori, Boyang Zhang, Takashi Okada, Darambazar Gantulga, Putra Santoso, Chiaki Masuda, Toshihiko YadaAbstract:Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.
-
paraventricular NUCB2 nesfatin 1 supports oxytocin and vasopressin neurons to control feeding behavior and fluid balance in male mice
Endocrinology, 2016Co-Authors: Masanori Nakata, Masatomo Mori, Boyang Zhang, Takashi Okada, Darambazar Gantulga, Putra Santoso, Chiaki Masuda, Toshihiko YadaAbstract:Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.
-
paraventricular NUCB2 nesfatin 1 is directly targeted by leptin and mediates its anorexigenic effect
Biochemical and Biophysical Research Communications, 2015Co-Authors: Gantulga Darambazar, Masanori Nakata, Masatomo Mori, Takashi Okada, Lei Wang, Atsumi Shinozaki, Megumi Motoshima, Toshihiko YadaAbstract:Abstract An adipokine leptin plays a central role in the regulation of feeding and energy homeostasis via acting on the hypothalamus. However, its downstream neuronal mechanism is not thoroughly understood. The neurons expressing nucleobindin-2 (NUCB2)-derived nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) have been implicated in feeding and energy homeostasis. The present study aimed to explore the role of PVN NUCB2/nesfatin-1 in the leptin action, by using adeno-associated virus (AAV) vectors encoding shRNA targeting NUCB2 (AAV-NUCB2-shRNA). Leptin directly interacted and increased cytosolic Ca 2+ in single neurons isolated from the PVN, predominantly in NUCB2/nesftin-1-immunoreactive neurons. Treatment with leptin in vivo and in vitro markedly increased NUCB2 mRNA expression in the PVN. Peripheral and central injections of leptin failed to significantly inhibit food intake in mice receiving AAV-NUCB2. These results indicate that PVN NUCB2/nesfatin-1 is directly targeted by leptin, and mediates its anorexigenic effect.
