Glucagon and hyperglycaemia in diabetes

A B S T R A C T Glucagon, in the setting of absolute or relative insulin deficiency, is thought to contribute to the pathogenesis of hyperglycaemia in diabetes, but much of the evidence is extrapolated from short-term studies to the long-term condition. In the present issue of Clinical Science, Li and coworkers report that infusion of glucagon raised fasting plasma glucose concentrations and impaired glucose tolerance over 4 weeks in mice, thus demonstrating a sustained glycaemic effect of hyperglucagonaemia. Nonetheless, compelling evidence that glucagon contributes to the pathogenesis of hyperglycaemia in diabetes awaits long-term selective reduction of glucagon secretion or action in humans. The existence of a second pancreatic hormone, one that raises plasma glucose concentrations, in addition to the glucose-lowering hormone insulin was deduced early in the 20th century and fully documented, and named glucagon, by the mid-20th century Glucagon is a 3500 Da peptide secreted from pancreatic islet α-cells into the hepatic portal venous circulation. The hormone increases hepatic glucose production by stimulating glycogenolysis and, particularly when gluconeogenic precursors are abundant, gluconeogenesis The role of glucagon in the physiological defence against hypoglycaemia is well established On the other hand, a role of glucagon, in the setting of absolute or relative insulin deficiency, in the pathogenesis of hyperglycaemia in diabetes, proposed by Unger and Orci [10] more than three decades ago, remains to be established conclusivel

Terbutaline and the Prevention of Nocturnal Hypoglycemia in Type 1 Diabetes

OBJECTIVE—Bedtime administration of 5.0 mg of the β2-adrenergic agonist terbutaline prevents nocturnal hypoglycemia but causes morning hyperglycemia in type 1 diabetes. We tested the hypothesis that 2.5 mg terbutaline prevents nocturnal hypoglycemia without causing morning hyperglycemia

Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes

A reduced sympathoadrenal response, induced by recent antecedent hypoglycemia, is the key feature of hypoglycemia-associated autonomic failure (HAAF) and, thus, the pathogenesis of iatrogenic hypoglycemia in diabetes. Understanding of the mechanism(s) of that reduced response awaits new insight into its basic molecular, cellular, organ, and whole-body physiology and pathophysiology in experimental models. In this issue of the JCI, McCrimmon and colleagues report that application of urocortin I (a corticotrophin-releasing factor receptor–2 agonist) to the ventromedial hypothalamus reduces the glucose counterregulatory response to hypoglycemia in rats (see the related article beginning on page 1723). Thus, hypothalamic urocortin I release during antecedent hypoglycemia is, among other possibilities, a potential mechanism of HAAF