Abnormalities of Endogenous Glucagon and Insulin in Unstable Diabetes

Abstract

The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virxual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.

Beta-cell function and metabolic control in insulin treated diabetics

“…A metabolic effect of residual beta-cell function has been demonstrated by several investigators Shima et al 1977;Reynolds et al 1977;Ludvigsson & Heding 1977a,b), while others have failed to demonstrate such a correla¬ tion (I keda et al 1975). Grajwer et al (1977) concluded in a cross-sectio¬ nal study of 35 children and juveniles with insulin dependent diabetes, that residual beta-cell function may facilitate good control, but that low or absent beta-cell function not always is associated with poor control.…”

Plasma glucagon responses to insulin-induced hypoglycemia and arginine in spontaneous non-insulin-dependent diabetes mellitus (NIDDM) rats, Otsuka Long Evans Tokushima Fatty (OLETF) strain

“…This is observed even in patients with IDDM who preserve a minimal residual function of pancreatic B cells (17,18), but pancreatic A cells fail to respond to hypoglycemia in patients without residual Bcell function. Thus, endogenous insulin, even in minute amounts, is related to glucagon secretion in response to hypoglycemia.…”

Nocturnal Cortisol Release During Hypoglycemia in Diabetes

“…The other four patients with normal glucagon profiles did not have raised plasma cortisol levels during the hypoglycemic phase. Although this could strengthen the argument against the adequacy of the hypoglycemic stimulus, many patients who have had diabetes for a number of years show impaired glucagon responses to hypoglycemia, 16 which could be an equally valid explanation for this observation. In contrast, the glucopenia was sufficient to evoke GH release in three and possibly four of the six patients.…”