Insulin supplementation elevates systolic blood pressure and arteriolar tone in mice with Type 2 diabetes

Hyperinsulinemia is frequently associated with hypertension but their interrelationship remains unclear. During the progression of Type 2 diabetes mellitus (T2DM) insulin secretion may decline due to loss of function of pancreatic β cells. We investigated the effect of insulin administration (daily i.p. injection of insulin, 1.67 mU/body weight (g) for 4‐wk) on blood pressure and also insulin‐induced changes in diameter of isolated resistance arteries in 36‐wk old db/db mice with T2DM. Compared to 12‐wk old db/db mice we found significantly reduced insulin levels (16.5±2.6 vs. 7.7±3.1 ng/ml) and severe hyperglycemia in 36‐wk old db/db mice. Also, compared to 12‐wk old db/db mice blood pressure (as measured by the tail cuff method) declined in 36‐wk old db/db mice and was found to be similar in aged‐matched control mice (118±13 vs. 119±5 mmHg). Interestingly, 4‐wk insulin treatment significantly elevated the blood pressure of 36‐wk old db/db mice (151±14 mmHg), to a level similar to what was found in 12‐wk old db/db mice (146±8 mmHg). In isolated skeletal muscle arterioles, incubation with insulin (30 min, 10 μg/ml) elicited significantly enhanced myogenic tone in 36‐wk old db/db mice (from 25±14% to 51±11% at 80 mmHg), but not in age‐matched controls. Thus we suggest that insulin, due to its vasoconstrictor effect on arterioles may elevate blood pressure in mice with Type 2 diabetes. (AHA 0735540T and NIH NHLBI 43023)