Glucagon production, effect

Glucagon, a peptide of 29 amino acids, is a product of the A cells of the pancreas. It is the antagonist of insulin and, like insulin, mainly influences carbohydrate and lipid metabolism. Its effects are each opposite to those of insulin. Glucagon mainly acts via the second messenger cAMP (see p. 384). 

Glucagon is sometimes useful for reversing the cardiac effects of an overdose of B-blocking agents because of its ability to increase cAMP production in the heart. However, it is not clinically useful in the treatment of cardiac failure. 

TABLE 23-4 Effects of Glucagon on Blood Glucose Production and Release of Glucose by the Liver... 

Several peptide products used in the treatment of diabetes mellitus, in addition to insulin, are currently administered by subcutaneous injection and these drugs are candidates for development of nasal formulations. Glucagon-like peptide-1 (GLP-l)-related peptides stimulate the insulin response to glucose and diminish the release of glucagon after a meal. These effects diminish the excessive postprandial increase in glucose observed after a meal in persons with type 2 diabetes mellitus. GLP-1-related peptides must be administered by subcutaneous injection before meals in order to be effective. This requirement for injection before each meal is likely to impact the utilization of these products by persons with type 2 diabetes. Exendin-4 is a GLP-1-related peptide with a molecular mass of 4.2 kDa. The development of a GLP-1-related peptide nasal formulation containing an absorption enhancer would allow patients to scll-administer one of these drugs just before a meal without the need for a subcutaneous injection. 

The islet cells of the pancreas synthesize and secrete insulin and glucagon. These hormones are important in regulating glucose uptake and use, as well as in other aspects of energy metabolism. Problems in the production and effects of insulin are typical of a disease known as diabetes mellitus. Diabetes mellitus can be categorized into two primary forms type 1 diabetes, which is caused by an absolute deficiency of insulin, and type 2 diabetes, which is caused by a decrease in peripheral insulin effects, combined with abnormal insulin release. 

The function of somatostatin in digestive processes is unclear. It inhibits the production of both insulin and glucagon, and these effects are believed to be local. 

In the liver, isoprenaline-stimulated adenylate cyclase has been found to be located almost exclusively on the surface of the parenchymal cells, with little or no deposit on the surface of the reticulo-endothelial cells. In contrast, the predominant effect of glucagon resulted in the deposition of reaction product on the reticulo-endothelial cell surface, although deposits were also present on the parenchymal cells. In the presence of F , there were substantial deposits on the surface of both types of cells. These results demonstrate that distinct enzyme systems are present in parenchymal and reticulo-endothelial cells. No theories concerning the function of adenylate cyclase in the liver have considered its role in the endothelial cells which act mainly on phagocytes. These cells contribute 35% of the cells in the liver and can be expected to contribute substantially to biochemical measurements of adenylate cyclase activity and cyclic AMP concentrations when liver slices, homogenates, or cell fractions constitute the enzyme source. 

Fig. 1. Effects of lack of glucagon ( ), catecholamine ( ), growth hormone (A), and cortisol (O) responses on counter-regulatory changes in glucose production (top) and glucose utilization (bottom) in non-diabetic volunteers. (Source Gerich, 1988.)...

---