Glucose regulation of glucagon secretion independent of B cell activity

To investigate whether glucose has an effect on the pancreatic A cell independent of intraislet or paracrine B cell mediation, we have tested the ability of changes in plasma glucose (PG) level to influence the acute glucagon response (AGR) to 5 g of intravenous arginine in 8 C-peptide negative insulin dependent diabetics (IDD). Insulin was infused (1 mU/kg/min) for a 90 min basal period during which PG levels were maintained constant by the glucose clamp technique. Basal AGR was then determined. In 4 of the diabetics, the PG level was subsequently lowered to a new steady state and, in 2 diabetics, PG level was raised. In 2 additional IDDs, two manipulations in PG level were carried out (PG ranges 51-390 mg/dl). The same insulin infusion was continued throughout. The acute glucagon response to arginine was determined at each PG level. The ability of unit changes in PG to influence (modulate) the AGR (MdIRG) was calculated as the difference in AGRs divided by the PG difference. MdIRG was consistent between diabetics (means +/- SEM = 2.1 +/- 0.2) and was independent of both direction and magnitude of the PG change. Thus, in vivo, in man, glucose has an effect on the pancreatic A cell which is independent of intraislet B cell influences.