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Klaas R Westerterp - One of the best experts on this subject based on the ideXlab platform.

  • gluconeogenesis and energy expenditure after a high protein carbohydrate free diet
    The American Journal of Clinical Nutrition, 2009
    Co-Authors: Margriet A B Veldhorst, Margriet S Westerterpplantenga, Klaas R Westerterp
    Abstract:

    Background: High-protein diets have been shown to increase energy expenditure (EE). Objective: The objective was to study whether a high-protein, carbohydrate-free diet (H diet) increases gluconeogenesis and whether this can explain the increase in EE. Design: Ten healthy men with a mean (6SEM) body mass index (in kg/m 2 ) of 23.0 6 0.8 and age of 23 6 1 y received an isoenergetic H diet (H condition; 30%, 0%, and 70% of energy from protein, carbohydrate, and fat, respectively) or a normal-protein diet (N condition; 12%, 55%, and 33% of energy from protein, carbohydrate, and fat, respectively) for 1.5 d according to a randomized crossover design, whereas EE was measured in a respiration chamber. Endogenous glucose production (EGP) and fractional gluconeogenesis were measured via infusion of [6,6- 2 H2]glucose and ingestion of 2 H2O; absolute gluconeogenesis was calculated by multiplying fractional gluconeogenesis by EGP. Body glycogen stores were lowered at the start of the intervention with an exhaustive glycogen-lowering exercise test. Results: EGP was lower in the H condition than in the N condition (181 6 9 compared with 226 6 9 g/d; P , 0.001), whereas fractional gluconeogenesis was higher (0.95 6 0.04 compared with 0.64 6 0.03; P , 0.001) and absolute gluconeogenesis tended to be higher (171 6 10 compared with 145 6 10 g/d; P = 0.06) in the H condition than in the N condition. EE (resting metabolic rate) was greater in the H condition than in the N condition (8.46 6 0.23 compared with 8.12 6 0.31 MJ/d; P , 0.05). The increase in EE was a function of the increase in gluconeogenesis (DEE = 0.007 · Dgluconeogenesis 2 0.038; r = 0.70, R 2 = 0.49, P , 0.05). The contribution of Dgluconeogenesis to DEE was 42%; the energy cost of gluconeogenesis was 33% (95% CI: 16%, 50%). Conclusions: Forty-two percent of the increase in energy expenditure after the H diet was explained by the increase in gluconeogenesis. The cost of gluconeogenesis was 33% of the energy content of the produced glucose. Am J Clin Nutr doi: 10.3945/ajcn.2009.27834.

  • gluconeogenesis and energy expenditure after a high protein carbohydrate free diet
    The American Journal of Clinical Nutrition, 2009
    Co-Authors: Margriet A B Veldhorst, Margriet S Westerterpplantenga, Klaas R Westerterp
    Abstract:

    BACKGROUND: High-protein diets have been shown to increase energy expenditure (EE). Objective: The objective was to study whether a high-protein, carbohydrate-free diet (H diet) increases gluconeogenesis and whether this can explain the increase in EE. DESIGN: Ten healthy men with a mean (+/-SEM) body mass index (in kg/m(2)) of 23.0 +/- 0.8 and age of 23 +/- 1 y received an isoenergetic H diet (H condition; 30%, 0%, and 70% of energy from protein, carbohydrate, and fat, respectively) or a normal-protein diet (N condition; 12%, 55%, and 33% of energy from protein, carbohydrate, and fat, respectively) for 1.5 d according to a randomized crossover design, whereas EE was measured in a respiration chamber. Endogenous glucose production (EGP) and fractional gluconeogenesis were measured via infusion of [6,6-(2)H(2)]glucose and ingestion of (2)H(2)O; absolute gluconeogenesis was calculated by multiplying fractional gluconeogenesis by EGP. Body glycogen stores were lowered at the start of the intervention with an exhaustive glycogen-lowering exercise test. RESULTS: EGP was lower in the H condition than in the N condition (181 +/- 9 compared with 226 +/- 9 g/d; P < 0.001), whereas fractional gluconeogenesis was higher (0.95 +/- 0.04 compared with 0.64 +/- 0.03; P < 0.001) and absolute gluconeogenesis tended to be higher (171 +/- 10 compared with 145 +/- 10 g/d; P = 0.06) in the H condition than in the N condition. EE (resting metabolic rate) was greater in the H condition than in the N condition (8.46 +/- 0.23 compared with 8.12 +/- 0.31 MJ/d; P < 0.05). The increase in EE was a function of the increase in gluconeogenesis (DeltaEE = 0.007 x Deltagluconeogenesis - 0.038; r = 0.70, R(2) = 0.49, P < 0.05). The contribution of Deltagluconeogenesis to DeltaEE was 42%; the energy cost of gluconeogenesis was 33% (95% CI: 16%, 50%). CONCLUSIONS: Forty-two percent of the increase in energy expenditure after the H diet was explained by the increase in gluconeogenesis. The cost of gluconeogenesis was 33% of the energy content of the produced glucose.

Bernard R. Landau - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of fructose 1 6 bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in zucker diabetic fatty rats
    Diabetes, 2006
    Co-Authors: Paul D Van Poelje, Visvanathan Chandramouli, Bernard R. Landau, Scott C Potter, Qun Dang, Mark D Erion
    Abstract:

    Gluconeogenesis is increased in type 2 diabetes and contributes significantly to fasting and postprandial hyperglycemia. We recently reported the discovery of the first potent and selective inhibitors of fructose 1,6-bisphosphatase (FBPase), a rate-controlling enzyme of gluconeogenesis. Herein we describe acute and chronic effects of the lead inhibitor, MB06322 (CS-917), in rodent models of type 2 diabetes. In fasting male ZDF rats with overt diabetes, a single dose of MB06322 inhibited gluconeogenesis by 70% and overall endogenous glucose production by 46%, leading to a reduction in blood glucose of >200 mg/dl. Chronic treatment of freely feeding 6-week-old male Zucker diabetic fatty (ZDF) rats delayed the development of hyperglycemia and preserved pancreatic function. Elevation of lactate (∼1.5-fold) occurred after 4 weeks of treatment, as did the apparent shunting of precursors into triglycerides. Profound glucose lowering (∼44%) and similar metabolic ramifications were associated with 2-week intervention therapy of 10-week-old male ZDF rats. In high-fat diet–fed female ZDF rats, MB06322 treatment for 2 weeks fully attenuated hyperglycemia without evidence of metabolic perturbation other than a modest reduction in glycogen stores (∼20%). The studies confirm that excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes and suggest that FBPase inhibitors may provide a future treatment option.

  • obesity and type 2 diabetes impair insulin induced suppression of glycogenolysis as well as gluconeogenesis
    Diabetes, 2005
    Co-Authors: Rita Basu, Visvanathan Chandramouli, Betty Dicke, Bernard R. Landau, Robert A. Rizza
    Abstract:

    To determine whether the hepatic insulin resistance of obesity and type 2 diabetes is due to impaired insulin-induced suppression of glycogenolysis as well as gluconeogenesis, 10 lean nondiabetic, 10 obese nondiabetic, and 11 obese type 2 diabetic subjects were studied after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Gluconeogenesis and glycogenolysis were measured using the deuterated water method. Before the clamp, when glucose and insulin concentrations differed among the three groups, gluconeogenesis was higher in the diabetic than in the obese nondiabetic subjects ( P P P P P P

  • effects of free fatty acids per se on glucose production gluconeogenesis and glycogenolysis
    Diabetes, 2003
    Co-Authors: Peter Staehr, Visvanathan Chandramouli, Bernard R. Landau, Ole Hothernielsen, Jens J. Holst, Henning Becknielsen
    Abstract:

    Insulin-independent effects of a physiological increase in free fatty acid (FFA) levels on fasting glucose production, gluconeogenesis, and glycogenolysis were assessed by administering [6,6-2H2]-glucose and deuteriated water (2H2O) in 12 type 1 diabetic patients, during 6-h infusions of either saline or a lipid emulsion. Insulin was either fully replaced (euglycemic group, n = 6), or underreplaced (hyperglycemic group, n = 6). During saline infusions, plasma FFA levels remained unchanged. Glucose concentrations decreased from 6.7 ± 0.4 to 5.3 ± 0.4 mmol/l and 11.9 ± 1.0 to 10.5 ± 1.0 mmol/l in the euglycemic and hyperglycemic group, respectively. Accordingly, glucose production declined from 84 ± 5 to 63 ± 5 mg · m−2 · min−1 and from 84 ± 5 to 68 ± 4 mg · m−2 · min−1, due to declining rates of glycogenolysis but unaltered rates of gluconeogenesis. During lipid infusions, plasma FFA levels increased twofold. In the euglycemic group, plasma glucose increased from 6.8 ± 0.3 to 7.8 ± 0.8 mmol/l. Glucose production declined less in the lipid study than in the saline study due to a stimulation of gluconeogenesis by 6 ± 1 mg · m−2 · min−1 and a decline in glycogenolysis that was 6 ± 2 mg · m−2 · min−1 less in the lipid study than in the saline study. In contrast, in the hyperglycemic group, there were no significant effects of elevated FFA on glucose production, gluconeogenesis, or glycogenolysis. In conclusion, a physiological elevation of plasma FFA levels stimulates glycogenolysis as well as gluconeogenesis and causes mild fasting hyperglycemia. These effects of FFA appear attenuated in the presence of hyperglycemia.

  • contributions of gluconeogenesis to glucose production in the fasted state
    Journal of Clinical Investigation, 1996
    Co-Authors: Bernard R. Landau, Visvanathan Chandramouli, John Wahren, William C Schumann, Karin Ekberg, Satish C Kalhan
    Abstract:

    Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.

Visvanathan Chandramouli - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of fructose 1 6 bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in zucker diabetic fatty rats
    Diabetes, 2006
    Co-Authors: Paul D Van Poelje, Visvanathan Chandramouli, Bernard R. Landau, Scott C Potter, Qun Dang, Mark D Erion
    Abstract:

    Gluconeogenesis is increased in type 2 diabetes and contributes significantly to fasting and postprandial hyperglycemia. We recently reported the discovery of the first potent and selective inhibitors of fructose 1,6-bisphosphatase (FBPase), a rate-controlling enzyme of gluconeogenesis. Herein we describe acute and chronic effects of the lead inhibitor, MB06322 (CS-917), in rodent models of type 2 diabetes. In fasting male ZDF rats with overt diabetes, a single dose of MB06322 inhibited gluconeogenesis by 70% and overall endogenous glucose production by 46%, leading to a reduction in blood glucose of >200 mg/dl. Chronic treatment of freely feeding 6-week-old male Zucker diabetic fatty (ZDF) rats delayed the development of hyperglycemia and preserved pancreatic function. Elevation of lactate (∼1.5-fold) occurred after 4 weeks of treatment, as did the apparent shunting of precursors into triglycerides. Profound glucose lowering (∼44%) and similar metabolic ramifications were associated with 2-week intervention therapy of 10-week-old male ZDF rats. In high-fat diet–fed female ZDF rats, MB06322 treatment for 2 weeks fully attenuated hyperglycemia without evidence of metabolic perturbation other than a modest reduction in glycogen stores (∼20%). The studies confirm that excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes and suggest that FBPase inhibitors may provide a future treatment option.

  • obesity and type 2 diabetes impair insulin induced suppression of glycogenolysis as well as gluconeogenesis
    Diabetes, 2005
    Co-Authors: Rita Basu, Visvanathan Chandramouli, Betty Dicke, Bernard R. Landau, Robert A. Rizza
    Abstract:

    To determine whether the hepatic insulin resistance of obesity and type 2 diabetes is due to impaired insulin-induced suppression of glycogenolysis as well as gluconeogenesis, 10 lean nondiabetic, 10 obese nondiabetic, and 11 obese type 2 diabetic subjects were studied after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Gluconeogenesis and glycogenolysis were measured using the deuterated water method. Before the clamp, when glucose and insulin concentrations differed among the three groups, gluconeogenesis was higher in the diabetic than in the obese nondiabetic subjects ( P P P P P P

  • effects of free fatty acids per se on glucose production gluconeogenesis and glycogenolysis
    Diabetes, 2003
    Co-Authors: Peter Staehr, Visvanathan Chandramouli, Bernard R. Landau, Ole Hothernielsen, Jens J. Holst, Henning Becknielsen
    Abstract:

    Insulin-independent effects of a physiological increase in free fatty acid (FFA) levels on fasting glucose production, gluconeogenesis, and glycogenolysis were assessed by administering [6,6-2H2]-glucose and deuteriated water (2H2O) in 12 type 1 diabetic patients, during 6-h infusions of either saline or a lipid emulsion. Insulin was either fully replaced (euglycemic group, n = 6), or underreplaced (hyperglycemic group, n = 6). During saline infusions, plasma FFA levels remained unchanged. Glucose concentrations decreased from 6.7 ± 0.4 to 5.3 ± 0.4 mmol/l and 11.9 ± 1.0 to 10.5 ± 1.0 mmol/l in the euglycemic and hyperglycemic group, respectively. Accordingly, glucose production declined from 84 ± 5 to 63 ± 5 mg · m−2 · min−1 and from 84 ± 5 to 68 ± 4 mg · m−2 · min−1, due to declining rates of glycogenolysis but unaltered rates of gluconeogenesis. During lipid infusions, plasma FFA levels increased twofold. In the euglycemic group, plasma glucose increased from 6.8 ± 0.3 to 7.8 ± 0.8 mmol/l. Glucose production declined less in the lipid study than in the saline study due to a stimulation of gluconeogenesis by 6 ± 1 mg · m−2 · min−1 and a decline in glycogenolysis that was 6 ± 2 mg · m−2 · min−1 less in the lipid study than in the saline study. In contrast, in the hyperglycemic group, there were no significant effects of elevated FFA on glucose production, gluconeogenesis, or glycogenolysis. In conclusion, a physiological elevation of plasma FFA levels stimulates glycogenolysis as well as gluconeogenesis and causes mild fasting hyperglycemia. These effects of FFA appear attenuated in the presence of hyperglycemia.

  • contributions of gluconeogenesis to glucose production in the fasted state
    Journal of Clinical Investigation, 1996
    Co-Authors: Bernard R. Landau, Visvanathan Chandramouli, John Wahren, William C Schumann, Karin Ekberg, Satish C Kalhan
    Abstract:

    Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.

Margriet A B Veldhorst - One of the best experts on this subject based on the ideXlab platform.

  • gluconeogenesis and energy expenditure after a high protein carbohydrate free diet
    The American Journal of Clinical Nutrition, 2009
    Co-Authors: Margriet A B Veldhorst, Margriet S Westerterpplantenga, Klaas R Westerterp
    Abstract:

    Background: High-protein diets have been shown to increase energy expenditure (EE). Objective: The objective was to study whether a high-protein, carbohydrate-free diet (H diet) increases gluconeogenesis and whether this can explain the increase in EE. Design: Ten healthy men with a mean (6SEM) body mass index (in kg/m 2 ) of 23.0 6 0.8 and age of 23 6 1 y received an isoenergetic H diet (H condition; 30%, 0%, and 70% of energy from protein, carbohydrate, and fat, respectively) or a normal-protein diet (N condition; 12%, 55%, and 33% of energy from protein, carbohydrate, and fat, respectively) for 1.5 d according to a randomized crossover design, whereas EE was measured in a respiration chamber. Endogenous glucose production (EGP) and fractional gluconeogenesis were measured via infusion of [6,6- 2 H2]glucose and ingestion of 2 H2O; absolute gluconeogenesis was calculated by multiplying fractional gluconeogenesis by EGP. Body glycogen stores were lowered at the start of the intervention with an exhaustive glycogen-lowering exercise test. Results: EGP was lower in the H condition than in the N condition (181 6 9 compared with 226 6 9 g/d; P , 0.001), whereas fractional gluconeogenesis was higher (0.95 6 0.04 compared with 0.64 6 0.03; P , 0.001) and absolute gluconeogenesis tended to be higher (171 6 10 compared with 145 6 10 g/d; P = 0.06) in the H condition than in the N condition. EE (resting metabolic rate) was greater in the H condition than in the N condition (8.46 6 0.23 compared with 8.12 6 0.31 MJ/d; P , 0.05). The increase in EE was a function of the increase in gluconeogenesis (DEE = 0.007 · Dgluconeogenesis 2 0.038; r = 0.70, R 2 = 0.49, P , 0.05). The contribution of Dgluconeogenesis to DEE was 42%; the energy cost of gluconeogenesis was 33% (95% CI: 16%, 50%). Conclusions: Forty-two percent of the increase in energy expenditure after the H diet was explained by the increase in gluconeogenesis. The cost of gluconeogenesis was 33% of the energy content of the produced glucose. Am J Clin Nutr doi: 10.3945/ajcn.2009.27834.

  • gluconeogenesis and energy expenditure after a high protein carbohydrate free diet
    The American Journal of Clinical Nutrition, 2009
    Co-Authors: Margriet A B Veldhorst, Margriet S Westerterpplantenga, Klaas R Westerterp
    Abstract:

    BACKGROUND: High-protein diets have been shown to increase energy expenditure (EE). Objective: The objective was to study whether a high-protein, carbohydrate-free diet (H diet) increases gluconeogenesis and whether this can explain the increase in EE. DESIGN: Ten healthy men with a mean (+/-SEM) body mass index (in kg/m(2)) of 23.0 +/- 0.8 and age of 23 +/- 1 y received an isoenergetic H diet (H condition; 30%, 0%, and 70% of energy from protein, carbohydrate, and fat, respectively) or a normal-protein diet (N condition; 12%, 55%, and 33% of energy from protein, carbohydrate, and fat, respectively) for 1.5 d according to a randomized crossover design, whereas EE was measured in a respiration chamber. Endogenous glucose production (EGP) and fractional gluconeogenesis were measured via infusion of [6,6-(2)H(2)]glucose and ingestion of (2)H(2)O; absolute gluconeogenesis was calculated by multiplying fractional gluconeogenesis by EGP. Body glycogen stores were lowered at the start of the intervention with an exhaustive glycogen-lowering exercise test. RESULTS: EGP was lower in the H condition than in the N condition (181 +/- 9 compared with 226 +/- 9 g/d; P < 0.001), whereas fractional gluconeogenesis was higher (0.95 +/- 0.04 compared with 0.64 +/- 0.03; P < 0.001) and absolute gluconeogenesis tended to be higher (171 +/- 10 compared with 145 +/- 10 g/d; P = 0.06) in the H condition than in the N condition. EE (resting metabolic rate) was greater in the H condition than in the N condition (8.46 +/- 0.23 compared with 8.12 +/- 0.31 MJ/d; P < 0.05). The increase in EE was a function of the increase in gluconeogenesis (DeltaEE = 0.007 x Deltagluconeogenesis - 0.038; r = 0.70, R(2) = 0.49, P < 0.05). The contribution of Deltagluconeogenesis to DeltaEE was 42%; the energy cost of gluconeogenesis was 33% (95% CI: 16%, 50%). CONCLUSIONS: Forty-two percent of the increase in energy expenditure after the H diet was explained by the increase in gluconeogenesis. The cost of gluconeogenesis was 33% of the energy content of the produced glucose.

J Radziuk - One of the best experts on this subject based on the ideXlab platform.

  • hepatic glucose uptake gluconeogenesis and the regulation of glycogen synthesis
    Diabetes-metabolism Research and Reviews, 2001
    Co-Authors: J Radziuk
    Abstract:

    Hepatic glycogen is replenished during the absorptive period postprandially. This repletion is prompted partly by an increased hepatic uptake of glucose by the liver, partly by metabolite and hormonal signals in the portal vein, and partly by an increased gluconeogenic flux to glycogen (Glyconeogenesis). There is some evidence that the direct formation of glycogen from glucose and that formed by gluconeogenic pathways is linked. This includes: (i) the inhibition of all glycogen synthesis, in vivo, when gluconeogenic flux is blocked by inhibitors; (ii) a dual relationship between glucose concentrations, lactate uptake by the liver and glycogen synthesis (by both pathways) which indicates that glucose sets the maximal rates of glycogen synthesis while lactate uptake determines the actual flux rate to glycogen; (iii) the decrease of both gluconeogenesis and glycogen synthesis by the biguanide, metformin; and (iv) correlations between increased gluconeogenesis and liver glycogen in obese patients and animal models. The degree to which the liver extracts portal glucose is not entirely agreed upon although a preponderance of evidence points to about a 5% extraction rate, following meals, which is dependent on a stimulation of glucokinase. This enzyme may be linked to the expression of other enzymes in the gluconeogenic pathway. Perivenous cells in the liver may induce additional gluconeogenesis in the periportal cells by increasing glycolytically produced lactate. A number of potential mechanisms therefore exist which could link glycogen synthesis from glucose and gluconeogenic substrate. Copyright © 2001 John Wiley & Sons, Ltd.

  • hepatic glucose uptake gluconeogenesis and the regulation of glycogen synthesis
    Diabetes-metabolism Research and Reviews, 2001
    Co-Authors: J Radziuk, S Pye
    Abstract:

    Hepatic glycogen is replenished during the absorptive period postprandially. This repletion is prompted partly by an increased hepatic uptake of glucose by the liver, partly by metabolite and hormonal signals in the portal vein, and partly by an increased gluconeogenic flux to glycogen (Glyconeogenesis). There is some evidence that the direct formation of glycogen from glucose and that formed by gluconeogenic pathways is linked. This includes: (i) the inhibition of all glycogen synthesis, in vivo, when gluconeogenic flux is blocked by inhibitors; (ii) a dual relationship between glucose concentrations, lactate uptake by the liver and glycogen synthesis (by both pathways) which indicates that glucose sets the maximal rates of glycogen synthesis while lactate uptake determines the actual flux rate to glycogen; (iii) the decrease of both gluconeogenesis and glycogen synthesis by the biguanide, metformin; and (iv) correlations between increased gluconeogenesis and liver glycogen in obese patients and animal models. The degree to which the liver extracts portal glucose is not entirely agreed upon although a preponderance of evidence points to about a 5% extraction rate, following meals, which is dependent on a stimulation of glucokinase. This enzyme may be linked to the expression of other enzymes in the gluconeogenic pathway. Perivenous cells in the liver may induce additional gluconeogenesis in the periportal cells by increasing glycolytically produced lactate. A number of potential mechanisms therefore exist which could link glycogen synthesis from glucose and gluconeogenic substrate.