Advances in pharmacology
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This chapter describes a physiological and profound effect of amylin to inhibit meal-related glucagon secretion. Glucagon is processed from a large precursor, proglucagon, in a tissue-specific manner in pancreatic alpha-cells. In addition to amino acid nutrient stimuli, glucagon is also secreted in response to stressful stimuli, such as hypoglycemia and hypovolemia. ⋯ Clinical studies have typically employed the amylinomimetic agent pramlintide. Studies of amylinomimetic effects on glucagon secretion include effects of rat amylin in anesthetized non-diabetic rats (Jodka et al., 2000; Parkes et al., 1999; Young et al., 1995), effects of rat amylin in isolated perfused rat pancreas (Silvestre et al., 1999), effects of pramlintide in anesthetized non-diabetic rats (Gedulin et al., 1997b,c,d, 1998), effects of pramlintide in patients with type l diabetes (Fineman et al., 1997a,b,c,d, 1998a; Holst, 1997; Nyholm et al., 1996, 1997a,b,c; Orskov et al., 1999; Thompson and Kolterman, 1997), and effects in patients with type 2 diabetes (Fineman et al., 1998b). In addition, effects of amylin antagonists have been observed in isolated preparations (Silvestre et al., 1996), and effects of antagonists or neutralizing antibody have been determined in whole-animal preparations (Gedulin et al., 1997a,e,f).