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Control of Glucose Production in vivo by Insulin and Glucagon

Alan D. Cherrington

10.1002/cphy.cp070225

Source: Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Assessment of Glucose Production in vivo
2 Glucagon and Glucose Production
2.1 Effects of Basal Glucagon
2.2 Effects of Increments in Glucagon
3 Insulin and Glucose Production
3.1 Effects of Insulin Deficiency
3.2 Effects of Increases in Insulin
3.3 Integration of Insulin and Glucagon's Effects
Figure 1. Figure 1.

The effect of glucagon deficiency on glucose production in the conscious overnight fasted dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the glucagon infusion was stopped. Glucose production was measured with 3‐3H‐glucose. Glucose was infused to maintain euglycemia. The difference between the closed and open symbols at the lower right represents the glucose infusion rate. Data were taken from reference 19.
Figure 2. Figure 2.

The relationship between hyperglycemia and net hepatic glucose output in conscious overnight fasted dogs with their plasma insulin and glucagon levels clamped at basal values using a pancreatic clamp. Each dot represents the mean of six dogs. Data taken from 29, 100, 116.
Figure 3. Figure 3.

The effect of glucagon excess on glucose production in the conscious overnight fasted dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the glucagon infusion was increased. Glucose production was measured with 3‐3H‐glucose. Data were taken from reference 135.
Figure 4. Figure 4.

The effect of glucagon excess on glucose production in the conscious overnight fasted human. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon through a peripheral vein. Glucose production was measured with 3‐3 H‐glucose. Data were redrawn from ref 84.
Figure 5. Figure 5.

The relationship between the estimated hepatic sinusoidal glucagon level (see text) and glucose production. The solid circles represent data from dogs (n = 5 or 6 for each point), and the open circles represent data from humans (n = 6 to 10 for each point). Data taken from references 19, 94, 53, 135, 97, 35, 84.
Figure 6. Figure 6.

The effect of increased glucagon on glycogenolysis and gluconeogenesis in the overnight fasted conscious dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the glucagon infusion rate was increased. Glycogenolysis and gluconeogenesis were assessed using the A‐V difference approach. Data taken from Wada et al. 135.
Figure 7. Figure 7.

The relationship between the estimated arterial plasma glucose level and the arterial plasma insulin level in the overnight fasted conscious dog. The basal glucose and insulin levels were 105 mg/dl and 11 μU/ml, respectively. An inhibitor of glycogenolysis was given at 0 min to reduce glucose production. Glucose was not replaced and was infused to create hyperglycemia in one group (open circles) or to maintain euglcyemia (dotted line). Data redrawn from ref 51.
Figure 8. Figure 8.

The effect of insulin deficiency on glucose production in the overnight fasted conscious dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the insulin infusion was stopped. Glucose production was measured using 3‐3H‐glucose. Data were redrawn from ref 17.
Figure 9. Figure 9.

The effect of insulin deficiency on glucose production in the human. Somatostatin (SRIF) was given along with a basal glucagon infusion through a peripheral vein beginning at 0 min. Glucose production was assessed with 3‐3H‐glucose. Data were redrawn from ref 114.
Figure 10. Figure 10.

Effects of a selective decrease in liver sinusoidal insulin on net hepatic glucose output in the overnight fasted conscious dog. Open symbols depict data from a control group, and closed symbols represent data from the group in which portal insulin was reduced. Data were redrawn from ref 119.
Figure 11. Figure 11.

Effects of insulin infusion through a leg vein on arterial plasma C‐peptide and glucagon levels in overnight fasted conscious dogs. Euglycemia was maintained by glucose infusion. The data were previously unpublished (A. D. Cherrington).
Figure 12. Figure 12.

Effects of insulin excess on glucose production in the overnight fasted conscious dog. Somatostatin (SRIF) was given along with basal portal replacement amounts of insulin and glucagon. At 0 min the insulin infusion rate was increased. Glucose was infused to maintain euglycemia. The difference between the closed and open symbols at the lower right represents the glucose infusion rate. Glucose production was measured using 3‐3H‐glucose. Data were redrawn from ref 125.
Figure 13. Figure 13.

Effects of insulin on glucose production in the overnight fasted human in the presence of euglycemia. The hepatic sinusoidal insulin level was calculated as described in the text. Data were redrawn from ref 69.
Figure 14. Figure 14.

The effects of a selective increase in arterial insulin on NHGO in the overnight fasted conscious dog. Open symbols depict data from a control group, and closed symbols represent data from the group in which arterial insulin was raised. Glucose was infused to maintain euglycemia. Data were redrawn from ref 117.
Figure 15. Figure 15.

The effects of a selective increase in hepatic portal vein insulin on NHGO in the overnight fasted conscious dog. Open symbols depict data from the control group, and closed symbols represent data from the group in which portal vein insulin was raised. Glucose was infused to maintain euglycemia. Data were redrawn from ref 117.
Figure 16. Figure 16.

The effects of alterations in liver sinusoidal insulin on hepatic glycogenolysis and gluconeogenesis in the overnight fasted conscious dog. Data were acquired in the presence of basal arterial and portal glucagon levels and basal arterial insulin concentrations. Euglycemia existed in all studies but the two that gave rise to the leftmost points, in which case the glucose level averaged 120 mg/dl. Data were taken from refs 46, 47, 117, 118, 119.
Figure 17. Figure 17.

The dose‐response relationships between the liver sinusoidal or arterial insulin level and hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) in the overnight fasted conscious dog. Data were taken from refs 61, 119, 16.


Figure 1.

The effect of glucagon deficiency on glucose production in the conscious overnight fasted dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the glucagon infusion was stopped. Glucose production was measured with 3‐3H‐glucose. Glucose was infused to maintain euglycemia. The difference between the closed and open symbols at the lower right represents the glucose infusion rate. Data were taken from reference 19.



Figure 2.

The relationship between hyperglycemia and net hepatic glucose output in conscious overnight fasted dogs with their plasma insulin and glucagon levels clamped at basal values using a pancreatic clamp. Each dot represents the mean of six dogs. Data taken from 29, 100, 116.



Figure 3.

The effect of glucagon excess on glucose production in the conscious overnight fasted dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the glucagon infusion was increased. Glucose production was measured with 3‐3H‐glucose. Data were taken from reference 135.



Figure 4.

The effect of glucagon excess on glucose production in the conscious overnight fasted human. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon through a peripheral vein. Glucose production was measured with 3‐3 H‐glucose. Data were redrawn from ref 84.



Figure 5.

The relationship between the estimated hepatic sinusoidal glucagon level (see text) and glucose production. The solid circles represent data from dogs (n = 5 or 6 for each point), and the open circles represent data from humans (n = 6 to 10 for each point). Data taken from references 19, 94, 53, 135, 97, 35, 84.



Figure 6.

The effect of increased glucagon on glycogenolysis and gluconeogenesis in the overnight fasted conscious dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the glucagon infusion rate was increased. Glycogenolysis and gluconeogenesis were assessed using the A‐V difference approach. Data taken from Wada et al. 135.



Figure 7.

The relationship between the estimated arterial plasma glucose level and the arterial plasma insulin level in the overnight fasted conscious dog. The basal glucose and insulin levels were 105 mg/dl and 11 μU/ml, respectively. An inhibitor of glycogenolysis was given at 0 min to reduce glucose production. Glucose was not replaced and was infused to create hyperglycemia in one group (open circles) or to maintain euglcyemia (dotted line). Data redrawn from ref 51.



Figure 8.

The effect of insulin deficiency on glucose production in the overnight fasted conscious dog. Somatostatin (SRIF) was given along with basal replacement amounts of insulin and glucagon intraportally. At 0 min the insulin infusion was stopped. Glucose production was measured using 3‐3H‐glucose. Data were redrawn from ref 17.



Figure 9.

The effect of insulin deficiency on glucose production in the human. Somatostatin (SRIF) was given along with a basal glucagon infusion through a peripheral vein beginning at 0 min. Glucose production was assessed with 3‐3H‐glucose. Data were redrawn from ref 114.



Figure 10.

Effects of a selective decrease in liver sinusoidal insulin on net hepatic glucose output in the overnight fasted conscious dog. Open symbols depict data from a control group, and closed symbols represent data from the group in which portal insulin was reduced. Data were redrawn from ref 119.



Figure 11.

Effects of insulin infusion through a leg vein on arterial plasma C‐peptide and glucagon levels in overnight fasted conscious dogs. Euglycemia was maintained by glucose infusion. The data were previously unpublished (A. D. Cherrington).



Figure 12.

Effects of insulin excess on glucose production in the overnight fasted conscious dog. Somatostatin (SRIF) was given along with basal portal replacement amounts of insulin and glucagon. At 0 min the insulin infusion rate was increased. Glucose was infused to maintain euglycemia. The difference between the closed and open symbols at the lower right represents the glucose infusion rate. Glucose production was measured using 3‐3H‐glucose. Data were redrawn from ref 125.



Figure 13.

Effects of insulin on glucose production in the overnight fasted human in the presence of euglycemia. The hepatic sinusoidal insulin level was calculated as described in the text. Data were redrawn from ref 69.



Figure 14.

The effects of a selective increase in arterial insulin on NHGO in the overnight fasted conscious dog. Open symbols depict data from a control group, and closed symbols represent data from the group in which arterial insulin was raised. Glucose was infused to maintain euglycemia. Data were redrawn from ref 117.



Figure 15.

The effects of a selective increase in hepatic portal vein insulin on NHGO in the overnight fasted conscious dog. Open symbols depict data from the control group, and closed symbols represent data from the group in which portal vein insulin was raised. Glucose was infused to maintain euglycemia. Data were redrawn from ref 117.



Figure 16.

The effects of alterations in liver sinusoidal insulin on hepatic glycogenolysis and gluconeogenesis in the overnight fasted conscious dog. Data were acquired in the presence of basal arterial and portal glucagon levels and basal arterial insulin concentrations. Euglycemia existed in all studies but the two that gave rise to the leftmost points, in which case the glucose level averaged 120 mg/dl. Data were taken from refs 46, 47, 117, 118, 119.



Figure 17.

The dose‐response relationships between the liver sinusoidal or arterial insulin level and hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) in the overnight fasted conscious dog. Data were taken from refs 61, 119, 16.

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Article Title: Control of Glucose Production in vivo by Insulin and Glucagon
 

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Alan D. Cherrington. Control of Glucose Production in vivo by Insulin and Glucagon. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 759-785. First published in print 2001. doi: 10.1002/cphy.cp070225