Interactions of glucagon and free fatty acids with insulin in control of glucose metabolism.

To study the interactions of physiological glucagon and free fatty acids (FFA) concentrations with insulin in the control of glucose metabolism, we determined in normal subjects the response of endogenous glucose production (EGP) and glucose utilization (Rd) to a progressive and moderate increase of insulinemia in the presence of glucagon and FFA levels either decreased (somatostatin [SRIF] and insulin infusion, C test) or maintained to normal postabsorptive values isolated (SRIF + insulin + glucagon infusion, G test; SRIF + insulin + Intralipid infusion, IL test) or in association (SRIF + insulin + glucagon + Intralipid infusion, IL + G test). Compared with the C test, maintenance of glucagon level had only small and inconsistent effects on glucose Rd, but induced a shift to the right of the dose-response curve to insulin of EGP (apparent ED50: C test, 10.9 mU.L-1; G test, 15.2 mU.L-1). Intralipid infusion resulted, whether glucagon was substituted or not, in a near total suppression of the insulin-induced increase of glucose Rd (Rd at the end of the tests: C test, 6.13 +/- 0.85 mg.kg-1.min-1; G test, 7.29 +/- 0.87 mg.kg-1.min-1; IL test, 3.30 +/- 0.65 mg.kg-1.min-1; IL + G test, 3.57 +/- 0.42 mg.kg-1.min-1). In the absence of glucagon, substitution Intralipid infusion also antagonized the action of insulin on EGP. However, this effect was no longer apparent when glucagon was replaced (dose-response curve to insulin of EGP during the G and the IL + G test were comparable).(ABSTRACT TRUNCATED AT 250 WORDS)