Rodney C. Ruhe

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.

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°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 and Insulin Secretion

Abstract 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 β-cell population may represent a means by which the endocrine pancreas is able to maintain appropriate insulin secretion during senescence.

Changes in Food Intake and Its Relationship to Weight Loss during Advanced Age

The results of extensive human and animal studies suggest that declining food intake and body weight observed in the later stages of life may be part of the normal progression of physiological decline observed during aging. Proposed etiologies cover a wide range of biological and psychological conditions. Studies in humans suggest an imbalance in homeostatic mechanisms governing hunger and satiety. That is, while older vs. younger individuals retain a similar drive (hunger) to eat, satiety occurs sooner during a meal in aged people and leads to an overall decrease in daily food intake. Age-related weight loss and a reduction in food intake have also been observed in laboratory animals. Alterations in neurochemical control of energy balance, especially as they relate to long-term regulation of food intake, have received much attention in recent years as the likely mechanism underlying age-related spontaneous weight loss. Age-related changes to neuroendocrine factors such as neuropeptide Y, GABA, CCK, leptin, and insulin have been linked to spontaneous weight loss observed during late life. This brief review provides an update on putative mechanisms underlying the dysregulation of feeding during advanced age that result in body weight loss.

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.

The Progression from Physiological Aging to Disease

Biologic aging is a complex and multifactoral phenomenon that is not well understood. Deficiencies in our understanding of the aging process are particularly evident with regard to the interface between normal deteriorative changes observed in all individuals (e.g., gray hair, loss of muscle mass, etc.) and clear, definable disease (e.g., cancer, Alzheimer’ s disease, etc.). For example, what factors contribute to the progression of the age-related dysregulation of glucose homeostasis into type II diabetes, and why does this disease occurs in only 8% of the older population, even though all individuals over the age of 80 yr show loss in insulin regulation?