Impaired insulin augmentation of GSIS in insulin-resistant subjects

Type 2 diabetes mellitus is characterized by insulin resistance and impaired insulin secretion, shown for example as an increase in the proinsulin-to-insulin ratio. Insulin production from beta-cells has shown to be stimulated by insulin itself through beta-cell specific insulin receptors.

Pancreatic islets from type 2 diabetics, however, have shown decreased expression of several insulin signaling proteins. Researchers at Joslin Diabetes Center in Boston, Massachusetts, USA have evaluated the effect of insulin on glucose-stimulated insulin secretion (GSIS) in insulin-resistant patients compared to insulin-sensitive healthy controls. They found insulin to potentiate GSIS in insulin-resistant subjects to a lesser extent than in normal subjects.

Since insulin is shown to suppress free fatty acid (FFA) concentrations and FFAs are assumed to stimulate or inhibit beta-cell function, it is difficult to determine whether the effect of insulin on beta-cell function is a direct or indirect effect. To examine this further, GSIS was assessed in healthy volunteers after pre-exposure to saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without Intralipid^® and heparin infusion. Pre-exposure to insulin significantly increased GSIS compared to sham clamp (pre-exposure to saline). However, GSIS was not different between the hyperinsulinemic clamp groups with or without Intralipid^® infusion. These studies show that insulin pre-exposure enhances GSIS independent of FFA in healthy humans. In addition, pre-exposure to insulin reduced the proinsulin-to-insulin ratio by 50%. This was only modestly attenuated after Intralipid^® administration. The results are consistent with a therapeutic effect of insulin in vivo to regulate beta-cell function in humans.

For these type of studies Mercodia offers the Mercodia human Insulin ELISA, specific for endogenous insulin. For measurement of total insulin or insulin analogues the Mercodia Iso-Insulin ELISA can be used.  This assay is specific for endogenous insulin as well as exogenously administered insulin or insulin analogues. The Mercodia Proinsulin ELISA may be used in combination with the Mercodia Insulin ELISA to determine the proinsulin-to-insulin ratio. All assays are well-characterized for accurate conclusions.

Halperin et al. (2012) Diabetes 61:301–309

Lopez et al. (2011) J Clin Endocrinol Metab 96: 3811–3821