Comprehensive Physiology Wiley Online Library

Insulin and Glucagon Secretion in vivo and its Neural Control

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Anatomy of the Endocrine Pancreas
1.1 Islet Cell Types
1.2 Vascular Supply
1.3 Innervation
2 Acute Regulation of Secretion
2.1 Secretion During Feeding
2.2 Secretion During Hypoglycemia
3 Chronic Adaptation of Secretion
3.1 Fasting
3.2 Obesity
3.3 Pregnancy
3.4 Partial β‐Cell Loss or Dysfunction
3.5 Human Diabetes Mellitus
4 Summary and Conclusion
Figure 1. Figure 1.

Distribution of α, β, and δ cells in a typical islet from the splenic lobe of rat pancreas. Note the predominance of β cells and the peripheral distribution of the α and δ cells. In islets from the duodenal lobe, F cells would replace α cells in this diagram.

[From Orci (211) with permission.]
Figure 2. Figure 2.

a: Low magnification (15×) of dog pancreas immunostained for galanin to identify sympathetic nerves. Localized intense staining defines three large islets and one‐large blood vessel. b: High magnification (120×) of a single dog islet immunostained for galanin to identify sympathetic nerves. Note the dense sympathetic innervation of the islet compared to the surrounding acinar tissue.

(Photos courtesy of Drs. C. B. Verchere and D. G. Baskin, unpublished.)
Figure 3. Figure 3.

Potentiation of the insulin response to isoproterenol by increasing plasma glucose level in humans. As plasma glucose level is increased by infusion of glucose, both the baseline insulin level and the acute insulin response (AIR) above that baseline are increased.

From Halter et al. 69 with permission.
Figure 4. Figure 4.

Relationship between magnitude of acute insulin response (AIR) to arginine and the prestimulus glucose level in normal human subjects (•), and non‐insulin‐dependent diabetes meltitus (NIDDM) patients (○), illustrating calculation of the slope of glycemic potentiation, AIRmax, and PG 50.

From Ward et al. 196 with permission.
Figure 5. Figure 5.

Change of pancreatic norepinephrine (NE) output in response to deoxyglucose (2‐DG)‐induced neuroglucopenia, hemorrhagic hypotension, or hypoxia in halothane‐anesthetized dogs. Note the increase of pancreatic norepinephrine output after deoxyglucose suggesting glucopenia‐induced activation of pancreatic sympathetic nerves.

From Havel et al. 83 with permission.
Figure 6. Figure 6.

Arterial plasma immunoreactive glucagon (IRG) response to insulin‐induced hypoglycemia in control dogs (glucose nadir = 1.9 ± 0.2 mM) and in cord‐section (CORDX), vagotomized (VAGX) dogs (glucose nadir = 1.0 ± 0.1 mM). In the absence of autonomic activation, the glucagon response is markedly reduced.

From Havel et al. 84 with permission.
Figure 7. Figure 7.

Insulin secretion from isolated perfused pancreas of control rats and of 15‐day pregnant rats as a function of perfusate glucose. Note the decreased glucose threshold and larger maximal response in pancreas from 15‐day pregnant rats.

From Parsons et al. 143 with permission.
Figure 8. Figure 8.

Insulin and glucose levels and responses to arginine before and twice during intravenous infusion of an insulin‐selective analogue of somatostatin. Note the lowered insulin level and response to arginine early during analogue infusion and their restoration later, when plasma glucose levels have doubled.

From Taborsky et al. 178 with permission.
Figure 9. Figure 9.

Insulin and glucose levels and responses to isoproterenol in type II diabetic patients before and after infusion of insulin to reduce fasting hyperglycemia. Reduction of hyperglycemia reduces the acute insulin response to isoproterenol.

From Halter et al. 69 with permission.
Figure 10. Figure 10.

Plasma glucose during induction of insulin resistance by 20 days of intravenous infusion with nicotinic acid (NA) in control baboons (•) and in baboons treated with 200 mg/kg of the beta‐cell toxin streptozotocin (Δ). In control animals, nicotinic acid infusion does not affect glucose level. In streptozotocin‐treated baboons, glucose levels are normal both before and after infusion of nicotinic acid.

From McCulloch et al. 122 with permission.
Figure 11. Figure 11.

Glucagon response to insulin‐induced hypoglycemia in nondiabetics (○) compared to patients with type I diabetes (•) for less than 1 month (left panel), 1 to 5 years (middle panel), and 14 to 31 years (right panel). Note progressive loss of the glucagon response with duration of diabetes.

From Bolli et al. 21 with permission.
Figure 12. Figure 12.

Plasma epinephrine (EPI), norepinephrine (NE), pancreatic polypeptide (PP), and glucagon (IRG) response in normal humans to a first (○) and third (•) episode of hypoglycemia of 50 mg/dl. Note reduction in autonomic and glucagon responses caused by prior episodes of hypoglycemia.

From Heller and Cryer 85 with permission.


Figure 1.

Distribution of α, β, and δ cells in a typical islet from the splenic lobe of rat pancreas. Note the predominance of β cells and the peripheral distribution of the α and δ cells. In islets from the duodenal lobe, F cells would replace α cells in this diagram.

[From Orci (211) with permission.]


Figure 2.

a: Low magnification (15×) of dog pancreas immunostained for galanin to identify sympathetic nerves. Localized intense staining defines three large islets and one‐large blood vessel. b: High magnification (120×) of a single dog islet immunostained for galanin to identify sympathetic nerves. Note the dense sympathetic innervation of the islet compared to the surrounding acinar tissue.

(Photos courtesy of Drs. C. B. Verchere and D. G. Baskin, unpublished.)


Figure 3.

Potentiation of the insulin response to isoproterenol by increasing plasma glucose level in humans. As plasma glucose level is increased by infusion of glucose, both the baseline insulin level and the acute insulin response (AIR) above that baseline are increased.

From Halter et al. 69 with permission.


Figure 4.

Relationship between magnitude of acute insulin response (AIR) to arginine and the prestimulus glucose level in normal human subjects (•), and non‐insulin‐dependent diabetes meltitus (NIDDM) patients (○), illustrating calculation of the slope of glycemic potentiation, AIRmax, and PG 50.

From Ward et al. 196 with permission.


Figure 5.

Change of pancreatic norepinephrine (NE) output in response to deoxyglucose (2‐DG)‐induced neuroglucopenia, hemorrhagic hypotension, or hypoxia in halothane‐anesthetized dogs. Note the increase of pancreatic norepinephrine output after deoxyglucose suggesting glucopenia‐induced activation of pancreatic sympathetic nerves.

From Havel et al. 83 with permission.


Figure 6.

Arterial plasma immunoreactive glucagon (IRG) response to insulin‐induced hypoglycemia in control dogs (glucose nadir = 1.9 ± 0.2 mM) and in cord‐section (CORDX), vagotomized (VAGX) dogs (glucose nadir = 1.0 ± 0.1 mM). In the absence of autonomic activation, the glucagon response is markedly reduced.

From Havel et al. 84 with permission.


Figure 7.

Insulin secretion from isolated perfused pancreas of control rats and of 15‐day pregnant rats as a function of perfusate glucose. Note the decreased glucose threshold and larger maximal response in pancreas from 15‐day pregnant rats.

From Parsons et al. 143 with permission.


Figure 8.

Insulin and glucose levels and responses to arginine before and twice during intravenous infusion of an insulin‐selective analogue of somatostatin. Note the lowered insulin level and response to arginine early during analogue infusion and their restoration later, when plasma glucose levels have doubled.

From Taborsky et al. 178 with permission.


Figure 9.

Insulin and glucose levels and responses to isoproterenol in type II diabetic patients before and after infusion of insulin to reduce fasting hyperglycemia. Reduction of hyperglycemia reduces the acute insulin response to isoproterenol.

From Halter et al. 69 with permission.


Figure 10.

Plasma glucose during induction of insulin resistance by 20 days of intravenous infusion with nicotinic acid (NA) in control baboons (•) and in baboons treated with 200 mg/kg of the beta‐cell toxin streptozotocin (Δ). In control animals, nicotinic acid infusion does not affect glucose level. In streptozotocin‐treated baboons, glucose levels are normal both before and after infusion of nicotinic acid.

From McCulloch et al. 122 with permission.


Figure 11.

Glucagon response to insulin‐induced hypoglycemia in nondiabetics (○) compared to patients with type I diabetes (•) for less than 1 month (left panel), 1 to 5 years (middle panel), and 14 to 31 years (right panel). Note progressive loss of the glucagon response with duration of diabetes.

From Bolli et al. 21 with permission.


Figure 12.

Plasma epinephrine (EPI), norepinephrine (NE), pancreatic polypeptide (PP), and glucagon (IRG) response in normal humans to a first (○) and third (•) episode of hypoglycemia of 50 mg/dl. Note reduction in autonomic and glucagon responses caused by prior episodes of hypoglycemia.

From Heller and Cryer 85 with permission.
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Gerald J. Taborsky. Insulin and Glucagon Secretion in vivo and its Neural Control. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 153-176. First published in print 2001. doi: 10.1002/cphy.cp070206