MODULATION OF IN-VIVO INSULIN ACTION BY DIETARY-PROTEIN DURING PREGNANCY

Rats were provided with a standard 20% protein diet or an isocaloric 8% protein diet from day 1 of gestation and were studied on clay 19 of pregnancy. Fetal numbers per dam were unchanged, but total fetal weight at day 19 of gestation was reduced by 10% (P < 0.001) in the 8% protein group. In the basal state, endogenous glucose production (R(a)) and muscle glucose uptake/phosphorylation were not significantly affected by dietary protein content. The glucose infusion rate required to maintain glycemia and R(a) during euglycemic-hyperinsulinemic clamp (insulin infusion rate of 4.17 mU.kg(-1).min(-)1()) were reduced in the 8% protein group by 17% (P < 0.05) and 76% (P < 0.001), respectively. Suppression of R(a) by insulin was not significant in the 20% protein group. Insulin-stimulated glucose disappearance (Rd) was 24% lower (P < 0.001) in the 8% protein group (25.0 +/- 0.8 mg.min(-1).kg(-1)) than in the 20% protein group (32.7 +/- 0.5 mg.min(-1).kg(-1)). The overall increment in muscle glucose utilization index (mean of 6 muscles) elicited by insulin was impaired by 38.1 +/- 4.0%. Insulin suppressed nonesterified fatty acid concentration (NEFA) by 83% (P < 0.001) and plasma triacylglycerol concentration (TAG) by 67% (P < 0.05) in the 20% protein group but evoked only a 43% (P < 0.01) decline in plasma NEFA and did not significantly suppress plasma TAG in the 8% protein group. The data demonstrate that restricting dietary protein intake during pregnancy leads to impaired action of insulin in vivo to 1) stimulate R(d), 2) stimulate glucose utilization by maternal muscle, and 3) suppress circulating NEFA and TAG. Impaired suppressibility of lipid fuel supply by insulin, together with partial substitution of fat for glucose as muscle energy substrate, in pregnant rats maintained on the low-protein diet may be viewed as a homoeostatic mechanism to spare glucose and restrict maternal protein loss while ensuring that the fetal protein supply is minimally compromised.