The impact of genetic hypertension on insulin secretion and glucoregulatory control in vivo:: studies with the TGR(mRen2)27 transgenic rat

Objective To examine the associations among hypertension, insulin secretion, glucose tolerance and insulin resistance in vivo. Design Glucose tolerance and insulin secretion during an intravenous glucose tolerance test and action of insulin on whole-body glucose kinetics in the post-absorptive state and during hyperinsulinaemia were examined in conscious, unrestrained TGR(mRen2) 27 rats and age-matched transgene-negative controls. Methods Glucose tolerance and insulin secretion were examined after intravenous administration of 500 mg glucose/kg body weight. Endogenous glucose production and whole-body glucose disposal were estimated using [3-H-3]-glucose during euglycaemic-hyperinsulinaemic clamping. Muscle glucose utilization was estimated using 2-deoxy-[1-H-3]-glucose. Results Despite there being higher insulin levels, whole-body glucose turnover was significantly lower in postabsorptive TGR(mRen2) 27 rats than it was in transgene-negative controls. This was associated with significant suppression of glucose uptake/phosphorylation by oxidative skeletal muscles. TGR(mRen2) 27 rats also exhibited significantly lower blood glucose levels, higher plasma insulin levels and higher rates of disappearance of glucose after intravenous administration of glucose. During hyperinsulinaemia, steady-state glucose infusion rates required to maintain euglycaemia in TGR(mRen2) 27 rats were significantly greater, indicating that an increase in whole-body action of insulin had occurred. This was due to significantly greater suppression of endogenous production of glucose: insulin-stimulated glucose disposal rates did not differ significantly between the two groups. Conclusions The results indicate that TGR(mRen2) 27 rats have an enhanced and sensitized insulin-secretory response to glucose, together with a greater than normal hepatic action of insulin. Insulin-mediated glucose disposal was not impaired. The results therefore do not support the hypothesis that hypertension plays a primary role in the development of insulin resistance. (C) 1998 Rapid Science Ltd.