Previous studies have demonstrated reduced in vivo insulin action in obese subjects compared with lean controls. However, little data is available on the relationship between degree of obesity and insulin action, and this relationship has not been shown to be independent of individual differences in maximal aerobic capacity. We studied 55 male Pima Indians and 35 male Caucasians with normal glucose tolerance. In vivo insulin action was measured using the hyperinsulinemic, euglycemic clamp technique at a plasma insulin concentration of approximately 100 microU/ml. Body composition was determined by densitometry, and maximal aerobic capacity was estimated using a graded exercise test. The results showed that degree of obesity was nonlinearly related to in vivo insulin action. In both Indians and Caucasians there was a significant decline in insulin action with increasing obesity up to a percent body fat of approximately 28-30%. Further increases in obesity in the Indians were not associated with significant changes in insulin action. Maximal aerobic capacity was positively linearly correlated with insulin action over the entire range of insulin action in both racial groups. Degree of obesity and maximal aerobic capacity were each independently associated with insulin action although these independent relationships were of marginal significance in the Caucasians. Surprisingly, individual differences in obesity and maximal aerobic capacity accounted for only half the variability observed in insulin action in these glucose tolerant subjects.

SUMMARY To assess factors in overweight persons that account for a tendency toward hypertension, 33 very obese women, 26 to 77 years of age, were studied. Blood pressures in these 33 women varied from low normal to mildly hypertensive. None of them had taken medication for high blood pressure, and none had diabetes mellitus. The effect of independent variables -age, body mass index (weight/height 2 ), fasting serum glucose levels, fasting serum insulin levels, and 24-hour urinary sodium excretion -on systolic and diastolic blood pressure was assessed. There was no correlation between sodium excretion and blood pressure. Age did not correlate with diastolic blood pressure but did correlate with systolic blood pressure when body mass index, serum glucose level, and insulin level were controlled. Diastolic blood pressure correlated with body mass index and serum glucose level, but only the latter remained significant when all independent variables were considered together. Both systolic and diastolic blood pressure were found to be significantly related to fasting serum insulin level (r = 0.47, p = 0.005 and r = 0.68, p < 0.001) even when age, weight, and serum glucose level were controlled (r = 0.41, p = 0.025 and r = 0.62, p < 0.001 respectively). The relation between serum insulin and blood pressure was more pronounced in those women with a family history of hypertension. These data indicate that insulin may play a major role in the regulation of blood pressure in obesity and that the previously accepted relation of weight to blood pressure may depend on blood levels of insulin. (Hypertension 7: 702-706, 1985) KEY WORDS • obesity • blood pressure • insulin • sodium excretion O BESITY is often associated with elevated blood pressure.1 ' 2 One of the factors thought to be responsible for this tendency toward hypertension is the often-observed hyperinsulinemia of obese subjects. 3•* This viewpoint is bolstered by observations that short-term insulin administration to normal subjects results in sodium retention, 5 -6 as well as increased blood pressure and heart rate. The present study examines the relation of age, weight, sodium intake, serum glucose level, and serum insulin level to blood pressure in markedly obese subjects. The results from this cross-sectional analysis indicate that obese persons with higher blood pressure tend to have the highest serum insulin levels and that this association is independent of age, weight, and serum glucose level.Subjects and Methods Thirty-three obese women, ranging in age from 26 to 77 years, who were at least 33% above calculated ideal weight, were studied in the Wayne State Univer-

SUMMARY This study was initiated to see if the insulin resistance, hyperinsulinemia, and hypertension that follow feeding nonnotensive Sprague-Dawley rats a fructose-rich diet could be prevented by letting rats run spontaneously in exercise wheel cages. Blood pressure in sedentary rats increased from (mean ± SEM) 125 ± 2 to 148 ± 3 mm Hg in response to 2 weeks of a high fructose diet, and this increment was significantly (p < 0.001) attenuated in exercising rats (from 121 ± 1 to 131 ± 2 mm Hg). In addition, mean (±SEM) plasma insulin concentration was lower in fructose-fed rats allowed to run spontaneously (44 ± 2 vs 62 ± 5 /xU/ml; p < 0.01). Finally, resistance to insulin-stimulated glucose uptake was assessed by determining the steady state plasma glucose response to a continuous glucose and exogenous Insulin infusion during a period in which endogenous insulin secretion was suppressed. The results of these studies indicated that the mean ( ± SEM) steady state plasma glucose concentration was significantly lower in the exercise-trained rats (127 ± 5 vs 168 ± 6 mg/dl; p < 0.001), despite tbe fact that the steady state plasma insulin levels were also lower in rats allowed to run spontaneously (75 ± 4 vs 90 ± 5 ftU/ml; p < 0.05). Thus, the ability of exercise-trained rats to stimulate glucose disposal was enhanced as compared with that of sedentary rats fed the same fructose-rich diet. These data demonstrate that the insulin resistance, hyperinsulinemia, and hypertension produced hi nonnotensive rats by feeding them a high fructose diet can be attenuated if rats are allowed to run spontaneously. I N a previous report we found that hypertension can be produced by feeding a high fructose diet to normal rats.1 Fructose-fed rats also develop resistance to insulin-stimulated glucose uptake and hyperinsulinemia, 1 -3 phenomena that have recently been identified as occurring in patients with hypertension.4 -7 Based on these findings, we raised the possibility that the changes in insulin action and concentration noted in fructose-fed rats with hypertension may play a role in the pathogenesis of the elevated blood pressure seen in this situation. In this context, we have previously demonstrated that insulin-stimulated glucose uptake is enhanced in exercise-trained rats 8 and that the hyperinsulinemia associated with feeding rats a high fructose diet is attenuated if rats are allowed to run spontaneously. 9Thus, in the present report, we tested the hypothesis that insulin resistance and hyperinsulinemia are involved in the development of hypertension in fructose-fed rats by comparing the effects of fructoserich diets on both insulin metabolism and blood pressure in sedentary rats with those seen in rats allowed to exercise spontaneously in running wheels. Materials and Methods General ProtocolMale Sprague-Dawley rats (Harlan, Indianapolis, IN, USA) were used for all experiments. The rats were approximately 6 weeks old and weighed approximately 150 g when the study was started. Prior to any manipulation of diet or level of ...

The effects of aging on various aspects of insulin secretion and action were studied in male Sprague-Dawley rats, maintained from 1 1/2 to 12 mo of age on conventional rat chow, sucrose-rich, or calorie-restricted diets. In chow-fed rats, islet volume increased as the animals grew from 1 1/2 to 12 mo of age, but glucose-stimulated insulin secretion (per volume islet) declined over the same interval. In addition, in vivo insulin-stimulated glucose utilization fell in these rats. However, the plasma insulin response to an oral glucose challenge was sufficient to prevent frank decompensation of glucose tolerance (presumably due to an increase in total pancreatic endocrine cell mass). All these changes, with the exception of the decline in glucose-stimulated insulin secretion per volume islet, were accentuated by feeding sucrose. Thus, 12-mo-old sucrose-fed rats had larger islets and higher plasma insulin levels in response to an oral glucose challenge, and the rats were more insulin-resistant than chow-fed rats. However, glucose-stimulated insulin release per volume islet was similar in 12-mo-old chow-fed and sucrose-fed rats. In contrast, calorie restriction led to an amelioration in all but one of the age-related changes, i.e., islets from calorie-restricted rats were comparable in size to those of 2-mo-old rats, the animals had lower plasma insulin levels in response to an oral glucose load, and they were less insulin resistant than the other two groups of 12-mo-old rats. On the other hand, glucose-stimulated insulin secretion per volume islet was similar to that of the other 12-mo-old rats. These results suggest that aging leads to marked changes in both insulin secretion and insulin action. The decline in glucose-stimulated insulin secretion per unit endocrine pancreas appears to be an inevitable consequence of the aging process. In contrast, the age-related changes in islet size, insulin response to a glucose load, and in vivo insulin-stimulated glucose uptake are extremely responsive to variations in amount and kind of calories. DIABETES 32:175-180, February 1983.