Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction.

Abstract

A B S T R A C T The current study was conducted to determine if physical activity and/or weight control could influence the age-related decrease in beta cell insulin response noted in earlier studies. As such, virgin, male Sprague-Dawley rats were maintained in our facility for 1 yr on three differential experimental programs: in the first group, control rats lived under standard laboratory conditions; the second group ofrats ran several miles a day in exercise wheels; and the third group was given a calorie-restricted diet designed to keep the rats weight-matched with the exercising rats. The results showed that the 12-mo-old sedentary control rats weighed an average of 800 g. From the time these rats were 4 mo old, they were significantly hyperinsulinemic, with mean (±SEM) serum insulin levels of 55±6 ,uU/ml compared with their base-line levels at 1Y2 mo of 20±3,uU/ml. Morphological studies on the pancreas of these rats at the end of the year revealed enlarged, multilobulated, fibrotic islets. After collagenase digestion, the most normal-appearing islets from the 12-mo-old controls were used for insulin secretion studies, these islets showed significantly reduced glucose-induced insulin release (0.83 ,uU insulin/min per volume islet) compared with islets from young rats (1.80 ,uU insulin/min per volume islet). In contrast, 12-mo-old exercised or calorie-restricted rats weighed -500 g and did not show the changes in serum insulin levels or pancreas pathology exhibited by the sedentary control animals. However, islets from the calorie-restricted group functioned in vitro no better than islets from the sedentary control group. Islets from the exercised rats were somewhat improved in this regard. In summary, we believe exercise and weight control diminishes the animals' need for insulinresulting in youthful-appearing islets after a year's Receivedfor publication 8January 1981 and in revisedform 16 March 1981. time. However, these regimes do not appear able to correct the beta cell decline in function previously de-scribed.

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

“…Prominent connective tissue proliferation was seen in these enlarged islets in which clusters of beta cells were widely separated from each other by strands of fibrotic tissue. These morphological features in the endocrine pancreas of the adult GK rat are reminiscent of those reported in the adult GK animals from the Sendaï colony [3] and the Stockholm colony [10], in the spontaneously hyperglycaemic OLETF rat [39], in the 1-year-old male Sprague-Dawley rat [40], in the Zucker fatty rat [41] and in the rabbit after pancreatic duct ligation [42]. In the GK rat, it is interesting to notice that the islet fibrosis is not a primary event but it can rather be considered as a consequence of the installation of hyperglycaemia since it is not detectable in the islets of the neonatal animals.…”

Length of metabolic normalization after rat islet cell transplantation depends on endocrine cell composition of graft and on donor age

“…Previous studies have shown that age reduces the islet secretory responses to glucose [10][11][12]20]. Selawry et al [21] reported that islets from 42-weekold donor rats failed to normalize plasma glucose levels in streptozotocin-diabetic rats while an identical number of islets from 10-week-old animals restored normoglycaemia in the majority of recipients.…”

“…The vicinity of glucagon-producing alpha cells could improve the survival of beta cells during culture or during the first posttransplantation days, thus leading to engraftment of a larger functional beta-cell mass than when the same number of beta cells is aggregated without alpha cells. The latter implants may -as a consequence -contain a marginally low beta-cell mass, and therefore become functionally inadequate at a later time, when insulin needs have increased as a result of the greater body weight and/or older age of the recipients [10,11,20]. It is also conceivable that the local release of glucagon amplifies the beta cells' secretory response to glucose, thus enhancing their homeostatic control.…”

Effect of age and environmental factors on insulin release from the perfused pancreas of the rat.

“…First among these is the problem of whether the age-related reduction in insulin secretion, noted in vitro, is an artifact of the process by which the islets are isolated. This concern is not entirely theoretical, as we know that there is often an increase in the connective tissue content of islets from older animals (2), and the possibility exists that islets from aging animals may be more susceptible to the action of collagenase than islets from young animals. The second question concerns the impact that an age-related decline in the secretory capacity of individual beta cells may have on the total secretory response of the animal.…”

“…Clearly, the insulin secreted by the total pancreas of an animal will depend not only on the insulin released from individual beta cells, but also on the total number of beta cells within the pancreas. Finally, we feel it is important to determine (2) and insulin resistant as they aged (2,6). Sucrose-fed rats.…”