Pancreatic Alpha and Beta Cell Function in Familial Dysbetalipoproteinemia

Abstract

Resistance to both insulin and glucagon have been considered as possible causes of primary hypertriglyceridemia. In the present research, we have compared insulin and glucagon secretion in five hyperlipidemic patients with familial dysbetalipoproteinemia with five normolipidemic control subjects matched for age, sex and adiposioty. Plasma insulin and glucagon concentrations mesaured during standard oral glucose tolerance and arginine infusion tests were similar in the two groups. Blood glucose fell transiently in the controls, but not in the patients, during the Himsworth test (100 g glucose orally plus 0.05 U insulin per kg body weight intravenously). There were no significant differences in plasma FFA concentrations and responses during all tests between the groups. The percentage reduction in plasma triglyceride concentration during infusion of arginine was similar in the two groups. These results suggest that the patients with familial dysbetalipoproteinemia were slightly less insulin sensitive than the controls. However, primary insensitivity to glucagon or insulin does not appear to be fundamental to the pathogenesis of hyperlipidemia in familial dysbetalipoproteinemia.

Lipotoxicity in a Vicious Cycle of Pancreatic Beta Cell Exhaustion

“…While fasting hyperinsulinemia predates hyperglycemia in most cases, suggesting that insulin resistance likely precedes beta cell dysfunction, it is unclear whether fasting insulin hypersecretion is a primary driver of insulin resistance or a consequence in the form of a compensatory whole-body response to insulin resistance [ 7 ]. It was also shown that primary insensitivity to insulin does not appear to be fundamental to the pathogenesis of hyperlipidemia in familial dysbetalipoproteinemia [ 8 ]. Therefore, it is of great research interest to clarify whether high blood lipids contribute to dysfunctional glucose-stimulated insulin secretion (GSIS).…”