Angiotensin II-induced hypertension in mice caused an increase in insulin secretion.

Objective And Design: Insulin action was determined in a mouse model of human hypertension via chronic angiotensin II administration followed by a glucose tolerance test.

Methods: Angiotensin II or saline was infused systemically into mice via osmotic pump for 2 or 4 weeks. In angiotensin II-treated mice versus saline controls we compared blood pressure, blood glucose, and serum insulin concentrations during an intravenous glucose tolerance test and assessed glucose transport and insulin signaling in muscle.

Results: Blood pressure increased at 2 and 4 weeks following angiotensin II treatment. Mice treated with angiotensin II for 4 weeks cleared a glucose bolus faster than mice treated with saline despite similar basal serum insulin concentrations. Upon glucose administration, the increase in serum insulin was greater in angiotensin II-treated mice, 38.8+/-6.5 pmol/l, compared to saline-treated mice, 21.8+/-2.9 pmol/l, but only at 4 weeks of angiotensin II treatment while no difference was observed at 2 weeks of angiotensin II administration. At 4 weeks of angiotensin II treatment, insulin signaling in the liver and in the skeletal muscle was not affected, since both the number of insulin receptors and phosphorylation of Akt were unchanged. Also at 4 weeks of angiotensin II treatment, ex vivo soleus muscle did not exhibit any change in basal and insulin-stimulated glucose uptake.

Conclusions: This study suggests that long-term angiotensin II treatment for 4 weeks enhances glucose-stimulated insulin secretion in mice. Angiotensin II-induced hyperinsulinemia may play a role in the development of insulin resistance in patients with hypertension.