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Jens J. Holst - One of the best experts on this subject based on the ideXlab platform.
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pancreatic α cell hyperplasia and hyperGlucagonemia due to a Glucagon receptor splice mutation
Endocrinology Diabetes & Metabolism Case Reports, 2016Co-Authors: Etienne Larger, Lars H Hansen, Richard W Gelling, Fumiatsu Yakushiji, Carolyn F Deacon, Ole D Madsen, Jacqueline Capeau, Pierre De Meyts, Nicolai Wewer J Albrechtsen, Jens J. HolstAbstract:: Glucagon stimulates hepatic glucose production by activating specific Glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, Glucagon secretion is regulated by concentrations of glucose and amino acids. Disruption of Glucagon signaling in rodents results in grossly elevated circulating Glucagon levels but no hypoglycemia. Here, we describe a patient carrying a homozygous G to A substitution in the invariant AG dinucleotide found in a 3' mRNA splice junction of the Glucagon receptor gene. Loss of the splice site acceptor consensus sequence results in the deletion of 70 nucleotides encoded by exon 9, which introduces a frame shift and an early termination signal in the receptor mRNA sequence. The mutated receptor neither bound 125I-labeled Glucagon nor induced cAMP production upon stimulation with up to 1 µM Glucagon. Despite the mutation, the only obvious pathophysiological trait was hyperGlucagonemia, hyperaminoacidemia and massive hyperplasia of the pancreatic α-cells assessed by histology. Our case supports the notion of a hepato-pancreatic feedback system, which upon disruption leads to hyperGlucagonemia and α-cell hyperplasia, as well as elevated plasma amino acid levels. Together with the Glucagon-induced hypoaminoacidemia in Glucagonoma patients, our case supports recent suggestions that amino acids may provide the feedback link between the liver and the pancreatic α-cells. LEARNING POINTS: Loss of function of the Glucagon receptor may not necessarily lead to the dysregulation of glucose homeostasis.Loss of function of the Glucagon receptor causes hyperaminoacidemia, hyperGlucagonemia and α-cell hyperplasia and sometimes other pancreatic abnormalities.A hepato-pancreatic feedback regulation of the α-cells, possibly involving amino acids, may exist in humans.
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the separate and combined impact of the intestinal hormones gip glp 1 and glp 2 on Glucagon secretion in type 2 diabetes
American Journal of Physiology-endocrinology and Metabolism, 2011Co-Authors: Asger Lund, Jens J. Holst, Tina Vilsboll, Jonatan I Bagger, Filip K KnopAbstract:Type 2 diabetes mellitus (T2DM) is associated with reduced suppression of Glucagon during oral glucose tolerance test (OGTT), whereas isoglycemic intravenous glucose infusion (IIGI) results in normal Glucagon suppression in these patients. We examined the role of the intestinal hormones glucose-dependent insulinotropic polypeptide (GIP), Glucagon-like peptide-1 (GLP-1), and Glucagon-like peptide-2 (GLP-2) in this discrepancy. Glucagon responses were measured during a 3-h 50-g OGTT (day A) and an IIGI (day B) in 10 patients with T2DM [age (mean ± SE), 51 ± 3 yr; body mass index, 33 ± 2 kg/m(2); HbA(1c), 6.5 ± 0.2%]. During four additional IIGIs, GIP (day C), GLP-1 (day D), GLP-2 (day E) and a combination of the three (day F) were infused intravenously. Isoglycemia during all six study days was obtained. As expected, no suppression of Glucagon occurred during the initial phase of the OGTT, whereas significantly (P < 0.05) lower plasma levels of Glucagon during the first 30 min of the IIGI (day B) were observed. The Glucagon response during the IIGI + GIP + GLP-1 + GLP-2 infusion (day F) equaled the inappropriate Glucagon response to OGTT (P = not significant). The separate GIP infusion (day C) elicited significant hypersecretion of Glucagon, whereas GLP-1 infusion (day D) resulted in enhancement of Glucagon suppression during IIGI. IIGI + GLP-2 infusion (day E) resulted in a Glucagon response in the midrange between the Glucagon responses to OGTT and IIGI. Our results indicate that the intestinal hormones, GIP, GLP-1, and GLP-2, may play a role in the inappropriate Glucagon response to orally ingested glucose in T2DM with, especially, GIP, acting to increase Glucagon secretion.
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Glucagon like peptide 1 but not glucose dependent insulinotropic peptide inhibits Glucagon secretion via somatostatin receptor subtype 2 in the perfused rat pancreas
Diabetologia, 2008Co-Authors: J. Heer, C. Rasmussen, D. H. Coy, Jens J. HolstAbstract:Aims/hypothesis The glucose-lowering effect of Glucagon-like peptide-1 (GLP-1) is based not only upon its potent insulinotropic actions but also on its ability to restrain Glucagon secretion. Surprisingly, the closely related glucose-dependent insulinotropic peptide (GIP) stimulates Glucagon release. We examined whether the islet hormone somatostatin, which strongly inhibits Glucagon secretion, is involved in this divergent behaviour.
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A meta-analysis of the effect of Glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans.
The Journal of clinical endocrinology and metabolism, 2001Co-Authors: Camilla Verdich, Jens J. Holst, Anne Flint, J.-p. Gutzwiller, Erik Näslund, Christoph Beglinger, Per M. Hellström, S. J. Long, Linda M. Morgan, Arne AstrupAbstract:Seven studies have now been published pertaining to the acute effect of iv administration of Glucagon-like peptide-1 (7-36) amide on ad libitum energy intake. In four of these studies energy intake was significantly reduced following the Glucagon-like peptide-1 infusion compared with saline. In the remaining studies, no significant effect of Glucagon-like peptide-1 could be shown. Lack of statistical power or low Glucagon-like peptide-1 infusion rate may explain these conflicting results. Our aim was to examine the effect of Glucagon-like peptide-1 on subsequent energy intake using a data set composed of subject data from previous studies and from two as yet unpublished studies. Secondly, we investigated whether the effect on energy intake is dose dependent and differs between lean and overweight subjects. Raw subject data on body mass index and ad libitum energy intake were collected into a common data set (n = 115), together with study characteristics such as infusion rate, duration of infusion, etc. From four studies with comparable protocol the following subject data were included if available: plasma concentrations of Glucagon-like peptide-1, subjective appetite measures, well-being, and gastric emptying rate of a meal served at the start of the Glucagon-like peptide-1 infusion. Energy intake was reduced by 727 kJ (95% confidence interval, 548-908 kJ) or 11.7% during Glucagon-like peptide-1 infusion. Although the absolute reduction in energy intake was higher in lean (863 kJ) (634-1091 kJ) compared with overweight subjects (487 kJ) (209-764 kJ) (P = 0.05), the relative reduction did not differ between the two groups (13.2% and 9.3%, respectively). Stepwise regression analysis showed that the Glucagon-like peptide-1 infusion rate was the only independent predictor of the reduction in energy intake during Glucagon-like peptide-1 (7-36) amide infusion (r = 0.4, P < 0.001). Differences in mean plasma Glucagon-like peptide-1 concentration on the Glucagon-like peptide-1 and placebo day (n = 43) were related to differences in feelings of prospective consumption (r = 0.40, P < 0.01), fullness (r = 0.38, P < 0.05), and hunger (r = 0.26, P = 0.09), but not to differences in ad libitum energy intake. Gastric emptying rate was significantly lower during Glucagon-like peptide-1 infusion compared with saline. Finally, well-being was not influenced by the Glucagon-like peptide-1 infusion. Glucagon-like peptide-1 infusion reduces energy intake dose dependently in both lean and overweight subjects. A reduced gastric emptying rate may contribute to the increased satiety induced by Glucagon-like peptide-1.
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Distribution of Glucagon-like peptide-1 and other preproGlucagon-derived peptides in the rat hypothalamus and brainstem
Neuroscience, 1997Co-Authors: Philip J. Larsen, Mads Tang-christensen, Jens J. Holst, Cathrine OrskovAbstract:Central administration of the preproGlucagon-derived peptide Glucagon-like peptide-1 significantly inhibits ingestion of food and water, and Glucagon-like peptide-1 binding sites are present in a multitude of central areas involved in the regulation of ingestional behaviour. To evaluate further the neuroanatomical organization of central Glucagon-like peptide-1 containing neuronal circuits with potential implications on ingestional behaviour, we carried out a series of experiments in the rat demonstrating the topographical sites of synthesis and processing of the preproGlucagon precursor followed by a chromatographic analysis of the processed fragments. In situ hybridization histochemistry revealed that preproGlucagon encoding messenger RNA was expressed in a single population of neurons in the caudal portion of the nucleus of the solitary tract. Gel chromatographic analysis of hypothalamic and brainstem tissue extracts revealed that the preproGlucagon precursor is processed in a fashion similar to that seen in the small intestine, preferentially giving rise to glicentin, Glucagon-like peptide-1 and Glucagon-like peptide-2. This single brain site of Glucagon-like peptide-1 synthesis was subsequently confirmed by immunohistochemical demonstration of Glucagon-like peptide-1-immunoreactive perikarya in the central and caudal parts of the nucleus of the solitary tract. Numerous sites containing Glucagon-like peptide-1 immunoreactive fibres were, however, discovered in the forebrain including hypothalamic, thalamic and cortical areas. The densest innervation by Glucagon-like peptide-1 immunoreactive nerve fibres was seen in the hypothalamic dorsomedial and paraventricular nuclei, but numerous Glucagon-like peptide-1 immunoreactive fibres were also seen throughout the periventricular strata of the third ventricle. Dual-labelling immunohistochemistry for tyrosine hydroxylase and Glucagon-like peptide-1 gave no evidence for co-localization of catecholamines and Glucagon-like peptide-1 in neurons of the lower brainstem. To identify neurons of the nucleus of the solitary tract that project to the hypothalamic paraventricular nucleus, the retrograde tracer FluoroGold was injected into this hypothalamic target and dual immunocytochemical identification of Glucagon-like peptide-1 and tyrosine hydroxylase-positive neurons was performed on brainstem sections containing retrogradely labelled perikarya. From this experiment it was seen that many of the retrogradely labelled neurons in the central portion of the nucleus of the solitary tract are catecholaminergic, while none is Glucagon-like peptide-1 immunoreactive. In contrast, most of the retrogradely labelled neurons of the caudal portion of the nucleus of the solitary tract contain Glucagon-like peptide-1. These observations further substantiate that Glucagon-like peptide-1 neurons of the solitary tract constitute a distinct non-catecholaminergic cell group which projects to many targets, one of which is the hypothalamic paraventricular nucleus.
Tina Vilsboll - One of the best experts on this subject based on the ideXlab platform.
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the role of Glucagon in the pathophysiology and treatment of type 2 diabetes
Mayo Clinic proceedings, 2018Co-Authors: Sofie Haedersdal, Asger Lund, Filip K Knop, Tina VilsbollAbstract:Type 2 diabetes is a disease involving both inadequate insulin levels and increased Glucagon levels. While Glucagon and insulin work together to achieve optimal plasma glucose concentrations in healthy individuals, the usual regulatory balance between these 2 critical pancreatic hormones is awry in patients with diabetes. Although clinical discussion often focuses on the role of insulin, Glucagon is equally important in understanding type 2 diabetes. Furthermore, an awareness of the role of Glucagon is essential to appreciate differences in the mechanisms of action of various classes of glucose-lowering therapies. Newer drug classes such as dipeptidyl peptidase-4 inhibitors and Glucagon-like peptide-1 receptor agonists improve glycemic control, in part, by affecting Glucagon levels. This review provides an overview of the effect of glucose-lowering therapies on Glucagon on the basis of an extensive PubMed literature search to identify clinical studies of glucose-lowering therapies in type 2 diabetes that included assessment of Glucagon. Clinical practice currently benefits from available therapies that impact the Glucagon regulatory pathway. As clinicians look to the future, improved treatment strategies are likely to emerge that will either use currently available therapies whose mechanisms of action complement each other or take advantage of new therapies based on an improved understanding of Glucagon pathophysiology.
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hyperGlucagonaemia analysed by Glucagon sandwich elisa nonspecific interference or truly elevated levels
Diabetologia, 2014Co-Authors: Nicolai Wewer J Albrechtsen, Filip K Knop, Bolette Hartmann, Simon Veedfald, Johanne Agerlin Windelov, Astrid Plamboeck, Kirstine N Bojsenmoller, Thomas Idorn, Bo Feldtrasmussen, Tina VilsbollAbstract:Aim/hypothesis HyperGlucagonaemia is a characteristic of several clinical conditions (e.g. end-stage renal disease (ESRD), type 2 diabetes, obesity before and after Roux-en-Y gastric bypass (RYGB) and vagotomy with pyloroplasty), but the molecular nature of ‘immunoreactive’ Glucagon is poorly characterised. The specific determination of fully processed, intact Glucagon requires a ‘sandwich’ assay employing a combination of antibodies directed against both N- and C-termini. We compared a novel assay for intact Glucagon with a highly sensitive C-terminal RIA (hitherto considered specific) to determine the extent to which the hyperGlucagonaemia measured in clinical samples was caused by authentic Glucagon. Methods We examined the performance of three commercial Glucagon ‘sandwich’ ELISAs. The ELISAwith the best overall performance was selected to compare Glucagon measurements in clinical samples with an established Glucagon RIA. Results The first assay performed poorly: there was high cross-reactivity with glicentin (22%) and a lack of sensitivity for Glucagon. The second and third assays showed minor cross-reactivity (1–5%) with oxyntomodulin and glicentin; however, the second assay had insufficient sensitivity for Glucagon in plasma (>10–20 pmol/l). Thus, only the third assay was suitable for measuring Glucagon concentrations in clinical samples. The ELISA and RIA measured similar Glucagon levels in healthy individuals. Measurements of samples from individuals with abnormally high (type 2 diabetes or obese) or very elevated (post vagotomy with pyloroplasty, post-RYGB) Glucagon levels were also similar in both assays. However, Glucagon levels in participants with ESRD were much lower when measured by ELISA than by RIA, indicating that the apparent hyperGlucagonaemia is not caused by fully processed intact Glucagon. Conclusions/interpretation For most purposes, sensitive Cterminal Glucagon RIAs are accurate. However, measurements may be spuriously high, at least in patients with renal disease. Trial Registration Samples from type 2 diabetic and normoglucose-tolerant patients before and 1 year after RYGB were from a study by Bojsen-Moller et al (trial registration number NCT 01202526). Samples from vagotomised and control individuals were from a study by Plamboeck et al (NCT01176890). Samples from ESRD patients were from a study by Idorn et al (NCT01327378).
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the separate and combined impact of the intestinal hormones gip glp 1 and glp 2 on Glucagon secretion in type 2 diabetes
American Journal of Physiology-endocrinology and Metabolism, 2011Co-Authors: Asger Lund, Jens J. Holst, Tina Vilsboll, Jonatan I Bagger, Filip K KnopAbstract:Type 2 diabetes mellitus (T2DM) is associated with reduced suppression of Glucagon during oral glucose tolerance test (OGTT), whereas isoglycemic intravenous glucose infusion (IIGI) results in normal Glucagon suppression in these patients. We examined the role of the intestinal hormones glucose-dependent insulinotropic polypeptide (GIP), Glucagon-like peptide-1 (GLP-1), and Glucagon-like peptide-2 (GLP-2) in this discrepancy. Glucagon responses were measured during a 3-h 50-g OGTT (day A) and an IIGI (day B) in 10 patients with T2DM [age (mean ± SE), 51 ± 3 yr; body mass index, 33 ± 2 kg/m(2); HbA(1c), 6.5 ± 0.2%]. During four additional IIGIs, GIP (day C), GLP-1 (day D), GLP-2 (day E) and a combination of the three (day F) were infused intravenously. Isoglycemia during all six study days was obtained. As expected, no suppression of Glucagon occurred during the initial phase of the OGTT, whereas significantly (P < 0.05) lower plasma levels of Glucagon during the first 30 min of the IIGI (day B) were observed. The Glucagon response during the IIGI + GIP + GLP-1 + GLP-2 infusion (day F) equaled the inappropriate Glucagon response to OGTT (P = not significant). The separate GIP infusion (day C) elicited significant hypersecretion of Glucagon, whereas GLP-1 infusion (day D) resulted in enhancement of Glucagon suppression during IIGI. IIGI + GLP-2 infusion (day E) resulted in a Glucagon response in the midrange between the Glucagon responses to OGTT and IIGI. Our results indicate that the intestinal hormones, GIP, GLP-1, and GLP-2, may play a role in the inappropriate Glucagon response to orally ingested glucose in T2DM with, especially, GIP, acting to increase Glucagon secretion.
Filip K Knop - One of the best experts on this subject based on the ideXlab platform.
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the role of Glucagon in the pathophysiology and treatment of type 2 diabetes
Mayo Clinic proceedings, 2018Co-Authors: Sofie Haedersdal, Asger Lund, Filip K Knop, Tina VilsbollAbstract:Type 2 diabetes is a disease involving both inadequate insulin levels and increased Glucagon levels. While Glucagon and insulin work together to achieve optimal plasma glucose concentrations in healthy individuals, the usual regulatory balance between these 2 critical pancreatic hormones is awry in patients with diabetes. Although clinical discussion often focuses on the role of insulin, Glucagon is equally important in understanding type 2 diabetes. Furthermore, an awareness of the role of Glucagon is essential to appreciate differences in the mechanisms of action of various classes of glucose-lowering therapies. Newer drug classes such as dipeptidyl peptidase-4 inhibitors and Glucagon-like peptide-1 receptor agonists improve glycemic control, in part, by affecting Glucagon levels. This review provides an overview of the effect of glucose-lowering therapies on Glucagon on the basis of an extensive PubMed literature search to identify clinical studies of glucose-lowering therapies in type 2 diabetes that included assessment of Glucagon. Clinical practice currently benefits from available therapies that impact the Glucagon regulatory pathway. As clinicians look to the future, improved treatment strategies are likely to emerge that will either use currently available therapies whose mechanisms of action complement each other or take advantage of new therapies based on an improved understanding of Glucagon pathophysiology.
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hyperGlucagonaemia analysed by Glucagon sandwich elisa nonspecific interference or truly elevated levels
Diabetologia, 2014Co-Authors: Nicolai Wewer J Albrechtsen, Filip K Knop, Bolette Hartmann, Simon Veedfald, Johanne Agerlin Windelov, Astrid Plamboeck, Kirstine N Bojsenmoller, Thomas Idorn, Bo Feldtrasmussen, Tina VilsbollAbstract:Aim/hypothesis HyperGlucagonaemia is a characteristic of several clinical conditions (e.g. end-stage renal disease (ESRD), type 2 diabetes, obesity before and after Roux-en-Y gastric bypass (RYGB) and vagotomy with pyloroplasty), but the molecular nature of ‘immunoreactive’ Glucagon is poorly characterised. The specific determination of fully processed, intact Glucagon requires a ‘sandwich’ assay employing a combination of antibodies directed against both N- and C-termini. We compared a novel assay for intact Glucagon with a highly sensitive C-terminal RIA (hitherto considered specific) to determine the extent to which the hyperGlucagonaemia measured in clinical samples was caused by authentic Glucagon. Methods We examined the performance of three commercial Glucagon ‘sandwich’ ELISAs. The ELISAwith the best overall performance was selected to compare Glucagon measurements in clinical samples with an established Glucagon RIA. Results The first assay performed poorly: there was high cross-reactivity with glicentin (22%) and a lack of sensitivity for Glucagon. The second and third assays showed minor cross-reactivity (1–5%) with oxyntomodulin and glicentin; however, the second assay had insufficient sensitivity for Glucagon in plasma (>10–20 pmol/l). Thus, only the third assay was suitable for measuring Glucagon concentrations in clinical samples. The ELISA and RIA measured similar Glucagon levels in healthy individuals. Measurements of samples from individuals with abnormally high (type 2 diabetes or obese) or very elevated (post vagotomy with pyloroplasty, post-RYGB) Glucagon levels were also similar in both assays. However, Glucagon levels in participants with ESRD were much lower when measured by ELISA than by RIA, indicating that the apparent hyperGlucagonaemia is not caused by fully processed intact Glucagon. Conclusions/interpretation For most purposes, sensitive Cterminal Glucagon RIAs are accurate. However, measurements may be spuriously high, at least in patients with renal disease. Trial Registration Samples from type 2 diabetic and normoglucose-tolerant patients before and 1 year after RYGB were from a study by Bojsen-Moller et al (trial registration number NCT 01202526). Samples from vagotomised and control individuals were from a study by Plamboeck et al (NCT01176890). Samples from ESRD patients were from a study by Idorn et al (NCT01327378).
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the separate and combined impact of the intestinal hormones gip glp 1 and glp 2 on Glucagon secretion in type 2 diabetes
American Journal of Physiology-endocrinology and Metabolism, 2011Co-Authors: Asger Lund, Jens J. Holst, Tina Vilsboll, Jonatan I Bagger, Filip K KnopAbstract:Type 2 diabetes mellitus (T2DM) is associated with reduced suppression of Glucagon during oral glucose tolerance test (OGTT), whereas isoglycemic intravenous glucose infusion (IIGI) results in normal Glucagon suppression in these patients. We examined the role of the intestinal hormones glucose-dependent insulinotropic polypeptide (GIP), Glucagon-like peptide-1 (GLP-1), and Glucagon-like peptide-2 (GLP-2) in this discrepancy. Glucagon responses were measured during a 3-h 50-g OGTT (day A) and an IIGI (day B) in 10 patients with T2DM [age (mean ± SE), 51 ± 3 yr; body mass index, 33 ± 2 kg/m(2); HbA(1c), 6.5 ± 0.2%]. During four additional IIGIs, GIP (day C), GLP-1 (day D), GLP-2 (day E) and a combination of the three (day F) were infused intravenously. Isoglycemia during all six study days was obtained. As expected, no suppression of Glucagon occurred during the initial phase of the OGTT, whereas significantly (P < 0.05) lower plasma levels of Glucagon during the first 30 min of the IIGI (day B) were observed. The Glucagon response during the IIGI + GIP + GLP-1 + GLP-2 infusion (day F) equaled the inappropriate Glucagon response to OGTT (P = not significant). The separate GIP infusion (day C) elicited significant hypersecretion of Glucagon, whereas GLP-1 infusion (day D) resulted in enhancement of Glucagon suppression during IIGI. IIGI + GLP-2 infusion (day E) resulted in a Glucagon response in the midrange between the Glucagon responses to OGTT and IIGI. Our results indicate that the intestinal hormones, GIP, GLP-1, and GLP-2, may play a role in the inappropriate Glucagon response to orally ingested glucose in T2DM with, especially, GIP, acting to increase Glucagon secretion.
A Kervran - One of the best experts on this subject based on the ideXlab platform.
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effects of Glucagon and Glucagon like peptide 1 7 36 amide on c cells from rat thyroid and medullary thyroid carcinoma ca 77 cell line
Endocrinology, 1996Co-Authors: A Crespel, F De Boisvilliers, L Gros, A KervranAbstract:Glucagon is known to stimulate calcitonin secretion by thyroid C cells over a wide range of concentrations, raising the possibility of its interaction with several types of receptors. This study was designed to characterize receptors that mediate the effect of Glucagon on a rat C cell line (CA-77). Binding studies, using radiolabeled [125I]Glucagon and [125I]Glucagon-like peptide-1-(7-36) amide ([125I]tGLP-1), to CA-77 plasma membranes demonstrated the presence of 1) a Glucagon receptor with a dissociation constant (Kd) of 2.3 nM and relative potencies for structurally related peptides as follows: Glucagon > oxyntomodulin > > tGLP-1; and 2) a tGLP-1 receptor with a Kd of 0.33 nM and relative potencies as follows: tGLP-1 > oxyntomodulin > Glucagon. Glucagon stimulated calcitonin secretion from CA-77 cells in a dose-dependent manner over 4 orders of magnitude, with a maximal response of 312% over the basal value and an ED50 close to 50 nM. tGLP-1 induced a calcitonin release over 2 orders of magnitude, with...
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Glucagon like peptide 1 7 36 amide oxyntomodulin and Glucagon interact with a common receptor in a somatostatin secreting cell line
Endocrinology, 1993Co-Authors: L Gros, D. Bataille, B Thorens, A KervranAbstract:Glucagon-like peptide-1(7-36)amide (tGLP-1), oxyntomodulin (OXM), and Glucagon are posttranslational end products of the Glucagon gene expressed in intestinal L-cells. In vivo, these peptides are potent inhibitors of gastric acid secretion via several pathways, including stimulation of somatostatin release. We have examined the receptors through which these peptides stimulate somatostatin secretion using the somatostatin-secreting cell line RIN T3. tGLP-1, OXM, and Glucagon stimulated somatostatin release and cAMP accumulation in RIN T3 cells to similar maximum levels, with ED50 values close to 0.2, 2, and 50 nM and 0.02, 0.3, and 8 nM, respectively. Binding of [125I]tGLP-1, [125I]OXM, and [125I]Glucagon to RIN T3 plasma membranes was inhibited by the three peptides, with relative potencies as follows: tGLP-1 > OXM > Glucagon. Whatever the tracer used, the IC50 for tGLP-1 was close to 0.15 nM and was shifted rightward for OXM and Glucagon by about 1 and 2-3 orders of magnitude, respectively. Scatchard ana...
Catherine Lee May - One of the best experts on this subject based on the ideXlab platform.
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Glucagon deficiency reduces hepatic glucose production and improves glucose tolerance in adult mice
Molecular Endocrinology, 2010Co-Authors: Aidan S Hancock, Jingxuan Liu, Mayumi Miller, Catherine Lee MayAbstract:The major role of Glucagon is to promote hepatic gluconeogenesis and glycogenolysis to raise blood glucose levels during hypoglycemic conditions. Several animal models have been established to examine the in vivo function of Glucagon in the liver through attenuation of Glucagon via Glucagon receptor knockout animals and pharmacological interventions. To investigate the consequences of Glucagon loss to hepatic glucose production and glucose homeostasis, we derived mice with a pancreas specific ablation of the α-cell transcription factor, Arx, resulting in a complete loss of the Glucagon-producing pancreatic α-cell. Using this model, we found that Glucagon is not required for the general health of mice but is essential for total hepatic glucose production. Our data clarifies the importance of Glucagon during the regulation of fasting and postprandial glucose homeostasis.