Glucagon does not increase plasma free fatty acid and glycerol concentrations in patients with noninsulin-dependent diabetes mellitus

Abstract

The study was initiated to determine whether physiological elevations of plasma glucagon would increase plasma FFA or glycerol concentrations in patients with noninsulin-dependent diabetes mellitus (NIDDM). To do this, patients were infused for 6 h with somatostatin (SRIF) alone or with SRIF plus glucagon. Furthermore, these studies were performed with an insulin infusion rate that maintains basal insulin levels or without any insulin infusion. Infusion of SRIF alone was associated with an increase in plasma FFA and glycerol concentrations, whereas hepatic glucose production and plasma glucose concentrations fell somewhat. When glucagon was added to SRIF, plasma FFA and glycerol concentrations were again increased, but to a significantly lesser extent. In addition, the addition of glucagon was associated with a modest increase in hepatic plasma glucose production and plasma glucose concentrations. In contrast, plasma FFA and glycerol concentrations fell when SRIF was infused in the presence of basal insulin levels. The decrease in FFA and glycerol levels tended to be accentuated when glucagon was also infused. It should be noted that the increases in hepatic glucose production and plasma glucose concentration after glucagon was added to SRIF were prevented when basal insulin levels were replaced. These results demonstrate that an increase in the plasma glucagon level comparable to that seen in patients with NIDDM was associated with lower, not higher, plasma FFA and glycerol concentrations in patients with NIDDM. Furthermore, these changes were seen in the absence of insulin or when basal insulin levels were replaced. Thus, the higher ambient plasma FFA and glycerol concentrations in patients with NIDDM do not appear to be secondary to increased plasma glucagon levels.