Effect of Age and Diet on Insulin Secretion and Insulin Action in the Rat

Abstract

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.

Long-term calorie restriction has minimal impact on brain metabolite and fatty acid profiles in aged rats on a Western-style diet

“…1), agrees with the CR phenotype generally reported (Ando et al, 2002;Faulks et al, 2006;Tacconi et al, 1991). However, CR did not affect plasma glucose or insulin (Table 2), which contrasts with improved insulin sensitivity in CR reported elsewhere (Bodkin et al, 1995;Lane et al, 1995;Reaven et al, 1983). Our high-sucrose diet may explain these results.…”

Characterization of sucrose-induced changes in cardiac phenotype

“…Although sucrose feeding reportedly results in insulin resistance and hyperinsulinaemia [18], the increase in serum insulin concentration observed in the present study was not significant. The 32% sucrose-fed rats exhibited, however, a significant rise in serum triglycerides that was prevented by BM13.907 and ciglitazone.…”

“…Intermittently fasted rats were compared with ad libitum-fed rats of greater heart weight. Moderate fasting can be regarded as physiological in rats and prevents the occurrence of the detrimental insulin resistance during growth of ad libitum-fed rats [18]. In the second approach, the diet of intermittently fasted and ad libitum-fed rats was supplemented with 32% sucrose.…”

Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity

“…Although variations in insulin sensitivity with aging have been reported [60][61][62], the development of insulin resistance also appears to be associated with the development of obesity, particularly of the central-visceral type [63][64][65], rather than due to aging per se. In our study, in HF diet-fed old female rats, chronic DHEA treatment reduces fasting insulin levels and, consequently, HOMA-IR, and it may be one of the possible mechanisms for DHEA to improve insulin sensitivity.…”