Effects of Intravenous and Oral Glucose Administration on Insulin Action in Human Fat Cells

The effects of various forms of glucose administration on insulin action were investigated in isolated human fat cells. Subcutaneous (s.c.) adipose tissue was obtained before and (1) 30 min (eight subjects) and 60 min (seven subjects) after an intravenous (i.v.) glucose load, and (2) after a 60-min continuous i.v. glucose infusion (five subjects). In addition, five subjects were reinvestigated before and 60 min after oral glucose ingestion. Lipolysis (glycerol release) and insulin receptor binding were determined. After all forms of i.v. glucose administration, adipocyte insulin binding was significantly reduced by 20% owing to a decrease in the high-affinity binding, whereas the concentrations of insulin producing the half-maximum inhibitions of basal and isoprenaline-induced rates of glycerol release were unaltered. Sixty minutes after oral glucose ingestion, insulin sensitivity increased 7–30-fold (P < 0.05–0.01) and high-affinityinsulin binding increased by 25% (P < 0.05). The maximum insulin-induced inhibitions ofbasal and isoprenaline-stimulated lipolysis were not altered after oral or i.v. glucose. The plasma level of glycerol was markedly and rapidly reduced after oral glucose, but the fall was slow and less pronounced after i.v. glucose. It is concluded that oral, but not i.v., glucose administration mediates a rapid increase in the antilipolytic potency of insulin in human fat cells in vitro. This may explain why antilipolysis in vivo is more pronounced after oral than after i.v. glucose challenge. Moreover, the lack of a clear correspondence between the observed changes in adipocyte insulin binding and sensitivity suggests the presence of separate short-term, glucose-mediated regulatory processes that operate both at the receptor and postreceptor levels of insulin action.