Biomedical subjects

R C Ruhe

Publications and source records attributed to R C Ruhe.

8 recordsLinked to original sources

PubMed2001

Use of antioxidant nutrients in the prevention and treatment of type 2 diabetes.

Type 2 diabetes, or non-insulin dependent diabetes mellitus (NIDDM), is increasingly common throughout the world. The World Health Organization has predicted that between 1997 and 2025, the number of diabetics will double from 143 million to about 300 million. The incidence of NIDDM is highest in economically developed nations, particularly the U.S., where approximately 6.5% of the population (17 million people) have either diagnosed or undiagnosed diabetes. The two most important factors contributing to the development of NIDDM are obesity and physical inactivity. The leading cause of mortality and morbidity in people with NIDDM is cardiovascular disease caused by macro- and microvascular degeneration. Current therapies for NIDDM focus primarily on weight reduction. Indeed, several investigations indicate that 65% to 75% of cases of diabetes in Caucasians could be avoided if individuals in this subgroup did not exceed their ideal weight. The success of this approach has been, at best, modest. An alternate approach to the control of Type 2 diabetes is to arrest the progress of the pathology until a cure has been found. To this end, some investigators suggest that dietary antioxidants may be of value. Several studies in humans and laboratory animals with NIDDM indicate that vitamin E and lipoic acid supplements lessen the impact of oxidative damage caused by dysregulation of glucose metabolism. In this brief review, we discuss the incidence, etiology, and current therapies for NIDDM and further explore the usefulness of dietary antioxidants in treating this disorder.

Antioxidants↗

PubMed1999

Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats.

We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26 degrees C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c-fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

Aging↗

PubMed1997

Altered cellular heterogeneity as a possible mechanism for the maintenance of organ function in senescent animals.

We tested the hypothesis that an alteration in the functional heterogeneity of cell populations (i.e., changes occurring in sensitivity and responsiveness to external stimuli among individual cells) may be a mechanism by which some organs are able to resist age-related decrements in function. To this end, changes in cytoplasmic free calcium concentration ([Ca2+]i) following glucose stimulation of individual pancreatic beta cells isolated from male F344 rats of ages 6, 12, and 26 mo were used as a model for evaluating responsiveness and sensitivity. Changes in [Ca2+]i of individual beta cells were monitored using fura-2 microspectrofluorimetry. No differences were observed in [Ca2+]i or in insulin secretion per beta cell among the age groups at any of the glucose concentrations. However, the percentage of beta cells that were responsive to a stimulatory glucose concentration (> 5.5 mM) was significantly greater in islets from the 26-mo-old rats (76%) as compared to the 6- and 12-mo-old animals (63% and 65%, respectively). Of the responsive beta cells, a significantly greater percentage of those from the 26-mo-old rats (72%) responded at the lowest stimulatory glucose concentration (7.5 mM) as compared to the 6- and 12-mo-old animals (58% and 60%, respectively). These data suggest that the maintenance of organ function in older rats at a level comparable to that of younger animals may be accomplished, in part, by an increase in the percentage of cells that are responsive to stimuli and/or by an increase in the sensitivity of the responsive cells.

Aging↗

PubMed1996

Effects of caloric restriction and source of dietary carbohydrate on glycemic status of the Fischer 344 rat.

The effects of caloric restriction and dietary carbohydrate source on the regulation of insulin secretion were evaluated in vivo and using islets of Langerhans isolated from 9-month-old male Fischer 344 rats. Serum glucose and insulin concentrations of rats fed a calorie-restricted diet for 6 months were significantly less than those of rats fed ad libitum, regardless of carbohydrate source. Rats fed diets containing fructose, either as a monosaccharide or as a component of a disaccharide, had generally greater serum insulin and glucose concentrations than rats fed diets containing no fructose. Glucose-stimulated insulin secretion by islets isolated from rats fed the restricted diet was significantly less than those of rats fed ad libitum. No differences in islet insulin secretion associated with carbohydrate source were observed. These results suggest that caloric restriction and the source of dietary carbohydrate can have significant effects on the glycemic status of the rat.

Animals↗

PubMed1995

Aging and insulin secretion.

Aging in mammals has often been associated with decreased insulin secretion and a subsequent deterioration in the ability to maintain glucose homeostasis. However, recent studies have demonstrated that factors such as disease, obesity, and physical activity more closely reflect diminished insulin secretion rather than aging per se. Thus, the purpose of this article is to review recent studies of how biological aging, i.e. the process independent of disease states such as type II diabetes, may affect insulin secretion. To this end, this review will address the impact of aging on insulin secretion in terms of in vivo and in vitro assessment, as well as possible age-related alterations in the hormonal and neural regulation of insulin secretion. Finally, this review describes some evidence that alterations in the functional heterogeneity of the beta-cell population may represent a means by which the endocrine pancreas is able to maintain appropriate insulin secretion during senescence.

Aging↗

PubMed1993

Stimulus-secretion coupling and insulin secretion in aging: evaluation of glucose oxidation and ATP-sensitive potassium channel responsiveness.

The purpose of this study was to evaluate possible age-related alterations in the glucose-stimulus/insulin-secretion coupling mechanism of islets of Langerhans. To this end, the interaction among insulin secretion, glucose oxidation, and ATP-sensitive potassium (K ATP) channel responsiveness was determined in islets of Langerhans isolated from 6-, 12-, and 26-month-old male Fischer 344 (F344) rats. Groups of 20 islets were incubated for 40 min at 37 degrees C in a buffer containing: (1) either 1.7 or 11.1 mM glucose; (2) 1.2 microM glyburide and either 1.7 or 11.1 mM glucose; (3) 5 microM epinephrine and 11.1 mM glucose; or (4) 1.2 microM glyburide, 5 microM epinephrine, and either 1.7 or 11.1 mM glucose. Insulin release of islets incubated in the presence of glyburide and 1.7 or 11.1 mM glucose was greater than that of islets incubated in glucose alone, while glucose oxidation did not increase. Epinephrine inhibited insulin release and glucose oxidation at 11.1 mM glucose and abolished glyburide-enhanced insulin release at 11.1 mM glucose. No effect of age was observed in any of the treatment categories. These results indicate that if age-related alterations are occurring in glucose-stimulus/insulin-secretion coupling, then such alterations are not associated with changes in K ATP channel-mediated responsiveness.

Adenosine Triphosphate↗

PubMed1992

Dietary sucrose enhances insulin secretion of aging Fischer 344 rats.

Male Fischer 344 rats, ages 6, 12 and 26 mo, were fed a diet containing either sucrose or cornstarch (66% by weight) for 4 mo. The effects of age and dietary sucrose on glucose-stimulated insulin secretion were evaluated in whole perfused pancreases and isolated islets of Langerhans, and by intra-arterial glucose administration. In addition, glucose responsiveness of beta-cells was measured by following the rate of glucose oxidation in isolated islets. There was no significant effect of age on glucose-stimulated insulin secretion of whole perfused pancreases and islets of Langerhans. There was, however, a significant main effect of sucrose feeding on insulin secretion. That is, whole perfused pancreases and islets of Langerhans isolated from rats fed sucrose vs. starch diets secreted more insulin in response to glucose. This effect was most pronounced in the 26-mo-old rats. In general, islet glucose oxidation rates, and responses to the in vivo glucose, did not differ among the groups. We conclude that alterations in glucose-stimulated insulin secretion with age more closely reflect changes in diet rather than aging per se.

Aging↗

PubMed1992

Age and gender effects on insulin secretion and glucose sensitivity of the endocrine pancreas.

Glucose-stimulated insulin secretion was evaluated in whole perfused pancreases and islets of Langerhans (90 to 110 microns diam) isolated from female and male Fischer 344 (F344) rats aged 6, 12, and 26 mo. Total glucose-stimulated (11.1 mmol/l) insulin release of whole perfused pancreases from male rats did not differ among age groups. In contrast, insulin secretion of 26-mo-old female rats was significantly greater than 6- and 12-mo-old female rats. Insulin secretion by islets of Langerhans incubated in glucose concentrations of 11.1, 16.7, and 22.2 mmol/l was greater in male rats compared with age-matched female animals at all three ages, and was greater in 6-vs. 26-mo-old male rats. Insulin secretion of female rats revealed some significant differences among the age groups, although no clear pattern was evident. Sensitivity of the islets to glucose was estimated from the rate of glucose oxidation. At incubation medium glucose concentrations of 11.1 mmol/l or higher, no effect of gender was observed, although the glucose oxidation rate of islets from male 26-mo-old rats was greater than that of islets from gender-matched 6-mo-old rats. These data indicate that in both the whole perfused pancreas and isolated islets of Langerhans, glucose-stimulated insulin secretion is not significantly altered with age or gender in the F344 rat. However, it appears that maintenance of insulin secretory capacity by aging male rats is achieved by enhancement of beta-cell sensitivity to glucose.

Aging↗