We studied the effects of short-term (5 days) and long-term (2 wk) high carbohydrate (75%) feedings on insulin binding to isolated adipocytes and insulin sensitivity in vivo in normal subjects. Ingestion of the high carbohydrate diet led to daylong hyperinsulinemia in both short- and long-term groups. Insulin binding to isolated adipocytes was decreased in both groups; in the short-term groups this decrease in insulin binding was caused by a decrease in the receptor affinity, whereas in the long-term group it was caused by a decrease in receptor number. On the other hand, despite this decrease in insulin binding, total in vivo insulin sensitivity was markedly improved in both groups. In conclusion, (1) the short-term adaptive response of the insulin receptor is a decrease in binding affinity whereas the long-term response is a decrease in receptor number, (2) sustained and chronic hyperinsulinemia can lead to a decrease in the number of cellular insulin receptors, (3) high carbohydrate diets lead to a general increase in insulin's ability to promote glucose removal from plasma, and (4) the paradox of enhanced insulin sensitivity in the face of decreased insulin binding can be explained if high carbohydrate diets also lead to an increase in the activity of steps in glucose metabolism distal to the insulin receptor.

Adipose Tissue↗

PubMedDate not supplied

Glyburide in non-insulin-dependent diabetes: an update.

Recent data suggest that non-insulin-dependent diabetes mellitus (NIDDM) may evolve in genetically predisposed individuals beginning with impaired peripheral glucose metabolism followed by insulin deficiency. Glyburide is an effective, long-acting, second-generation oral sulfonylurea introduced in the United States in 1984. In comparison with the first-generation sulfonylureas, glyburide is at least as effective, has a lower incidence of side effects, and may enhance postreceptor insulin activity to a greater degree. Glyburide can improve glycemic control, as evidenced by reduced fasting blood glucose concentrations and glycohemoglobin levels, without the inconvenience of insulin injections, the higher plasma insulin concentrations, and the additional training required to administer insulin. Because of its ability to enhance target tissue insulin action, glyburide also improves glycemic control in many NIDDM patients who have previously failed therapy with other sulfonylurea agents. Gluburide, as adjunctive therapy, may reduce the daily dosage needed by those who require insulin. Favorable pharmacokinetics and high inherent potency of glyburide often allow effective therapy when the drug is administered once a day.

Diabetes Mellitus, Type 2↗