Chromium,glucose tolerance,and diabetes

Summary Chromium functions in maintaining normal glucose tolerance primarily by regulating insulin action. In the presence of optimal amounts of biologically active chromium, much lower amounts of insulin are required. Glucose intolerance, related to insufficient dietary chromium, appears to be widespread. Improved chromium nutrition leads to improved sugar metabolism in hypoglycemics, hyperglycemics, and diabetics.     

Obestatin, obesity and diabetes

The high prevalence of obesity and diabetes will lead to higher rates of morbidity and mortality. It is well known that ghrelin plays a potential role in obesity and diabetes. Obestatin, a novel 23 amino acid amidated peptide encoded by the same gene that encodes ghrelin, was initially reported to have opposite actions to ghrelin in the regulation of food intake, emptying of the stomach and body weight. Recent work suggests that obestatin also regulate beta-cell survival and insulin secretion. The ghrelin-obestatin system is, therefore, a promising target for the developing of new drugs for the treatment of obesity and diabetes. This review summarizes the interrelationship between obestatin, obesity and diabetes.     

RAGE, diabetes, and the nervous system

Longstanding diabetes mellitus targets kidney, retina, and blood vessels, but its impact upon the nervous system is another important source of disability. Diabetic peripheral neuropathy is a serious complication of inadequately treated diabetes leading to sensory loss, intractable neuropathic pain, loss of distal leg muscles, and impairment of balance and gait. Diabetes has been implicated as a cause of brain atrophy, white matter abnormalities, and cognitive impairment and a risk factor for dementia. Recent studies have incriminated advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic nervous system complications. The availability of RAGE knockout mice and a competitive decoy for AGEs, soluble RAGE (sRAGE), has advanced our knowledge of the RAGE-mediated signalling pathways within the nervous system. They also provide hope for a future novel intervention for the prevention of diabetes-associated neurological complications. This review will discuss current knowledge of diabetes- and RAGE-mediated neurodegeneration, involving the distal-most level of epidermal nerve fibers in skin, major peripheral nerve trunks, dorsal root ganglia, spinal cord, and brain.     

Nutrient intake,adiposity, and diabetes.

To study the role of nutritional factors in the genesis of diabetes, estimations of blood sugar concentration, food intake, and adiposity (as body mass index; BMI) were carried out on three normal population samples--namely, 961 employees of Beecham Ltd, 1005 employees of the Greater London Council, and 1488 middle-aged male civil servants (Whitehall study). Blood sugar concentrations and indices of glucose tolerance correlated positively with the degree of adiposity but tended to be negatively correlated with total food energy intake and its component nutrients (total carbohydrate, sucrose, and fat). This inverse trend was largely accounted for by highly significant inverse correlations between food energy intake and adiposity, a relation found in both sexes and in all three population samples and which extended across the whole range of nutrient intake and BMI. These findings suggest that greater degrees of adiposity are associated with lower than average food energy intakes and hence lower total energy expenditures. The association of increased adiposity with low food energy consumption may indicate an underlying "low energy throughput" state, and it may be the mechanisms of this, as well as the obesity, that are responsible for disease.     

Obesity, diabetes mellitus, and liver fibrosis

Obesity is a global epidemic with more than 1 billion overweight adults and at least 300 million obese patients worldwide. Diabetes is characterized by a defect in insulin secretion or a decrease in sensitivity to insulin, which results in elevated fasting blood glucose. Both obesity and elevated fasting glucose are risk factors for nonalcoholic fatty liver disease, a disease spectrum that includes hepatic steatosis (nonalcoholic fatty liver), nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Increased adiposity and insulin resistance contribute to the progression from NASH to fibrosis through the development of a profibrotic mileau in the liver, including increased hepatocellular death, increased reactive oxygen species generation, and an altered adipokine/cytokine balance. This review will summarize recent advances in our understanding of the pathological interactions among excessive fat accumulation, insulin resistance, and hepatic fibrogenesis and discuss specific molecular pathways that may be of interest in the development of therapeutic interventions to prevent and/or reverse hepatic fibrosis.     

Oxidative stress, insulin signaling, and diabetes

Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. Experimental and clinical data suggest an inverse association between insulin sensitivity and ROS levels. Oxidative stress can arise from a number of different sources, whether disease state or lifestyle, including episodes of ketosis, sleep restriction, and excessive nutrient intake. Oxidative stress activates a series of stress pathways involving a family of serine/threonine kinases, which in turn have a negative effect on insulin signaling. More experimental evidence is needed to pinpoint the mechanisms contributing to insulin resistance in both type 1 diabetics and nondiabetic individuals. Oxidative stress can be reduced by controlling hyperglycemia and calorie intake. Overall, this review outlines various mechanisms that lead to the development of oxidative stress. Intervention and therapy that alter or disrupt these mechanisms may serve to reduce the risk of insulin resistance and the development of diabetes.     

Insulin-dependent diabetes, an autoimmune disease

In type I (insulin-dependent) diabetes evidence for an autoimmune process is now fully established. This is also true for a similar disease observed in the NOD mouse and the BB rat. In addition to circulating antipancreatic antibodies, we demonstrated T-lymphocyte mediated cellular immunity in both these diabetic animals and in the human. Immunological abnormalities precede the development of diabetes and may be responsible for beta cell alteration. Evidence for this interpretation appears stronger for cell-mediated than for humoral immunity. However, full demonstration and understanding of the relationship between anti-beta cell immunity and beta cell alteration still raise many unresolved problems.     

Temporal differences in bladder dysfunction caused by diabetes, diuresis, and treated diabetes in mice

Diabetic bladder dysfunction is a common complication of diabetes mellitus (DM) with poorly understood natural history. This study examined the temporal changes in bladder function 3, 9, 12, and 20 wk after induction of DM by streptozotocin (STZ) in male C57BL/6 mice compared with that in age-matched diabetic mice treated with insulin, 5% sucrose-induced diuretic mice, and sham-treated control mice. Conscious cystometrograms of mice were examined in addition to the measurements of micturition cycle. Diabetes resulted in decreased body weight. Bladder weight, urine output, bladder capacity, and compliance increased in the DM and diuretic groups. Peak voiding pressure (PVP) increased initially in both DM and diuretic mice. However, in DM mice, PVP dropped dramatically at and after 12 wk. Similar changes in the capacity, compliance, and emptying ability of the bladder were seen during the first 9 wk of the diabetes or diuresis, whereas significant decline in the emptying ability of the bladder was only seen in diabetes after 12 wk of disease in mice. Long-term insulin replacement effectively reversed most changes in bladder function. These results suggest that the transition from a compensated to a decompensated bladder dysfunction occurs 9-12 wk after induction of DM in mice by STZ.     

Sex hormones, insulin sensitivity, and diabetes mellitus

Sex differences and the role of gonadal hormones in modulating insulin sensitivity and glucose tolerance are of increasing interest and importance because of the increasing prevalence of type 2 diabetes mellitus and the metabolic abnormalities associated with aging. Body composition is closely associated with insulin sensitivity, and increased body fat, particularly in the visceral compartment, is a risk factor for developing type 2 diabetes mellitus. Sex differences in body composition and/or insulin sensitivity are evident in humans throughout the lifespan. Ovarian hormones influence insulin sensitivity across the menstrual cycle, during pregnancy, and in the menopausal transition. Similarly, estrogens and progestins used for contraception and hormone replacement therapy affect glucoregulation. Nonhuman primates and humans have similar life histories and reproductive characteristics. As a result, nonhuman primates provide a valuable model for investigating factors related to insulin sensitivity. Studies of nonhuman primates have contributed significantly to our understanding of sex differences and the influence of sex steroids in this context. This brief review surveys present knowledge of the sex differences in body composition, insulin sensitivity, and risk for development of type 2 diabetes mellitus derived from studies in humans and nonhuman primates. The influences of endogenous and exogenous gonadal steroids are emphasized.     

49,XXXXY syndrome with diabetes mellitus

49,XXXXY syndrome is a rare sex chromosome aneuploidy and characterized by mental retardation, skeletal defects, craniofacial anomalies and hypogonadism. The increased frequency of diabetes mellitus in patients with Klinefelter syndrome and other types of X-chromosome polysomy has been reported, but no cases of diabetes mellitus in adult with 49,XXXXY syndrome have been reported so far. We report an 18-year-old patient with 49,XXXXY syndrome accompanying diabetes mellitus.     

Endoplasmic reticulum stress, obesity and diabetes

The endoplasmic reticulum (ER) stress response, also commonly known as the unfolded protein response (UPR), is an adaptive response used to align ER functional capacity with demand. It is activated in various tissues under conditions related to obesity and type 2 diabetes. Hypothalamic ER stress contributes to inflammation and leptin/insulin resistance. Hepatic ER stress contributes to the development of steatosis and insulin resistance, and components of the UPR regulate liver lipid metabolism. ER stress in enlarged fat tissues induces inflammation and modifies adipokine secretion, and saturated fats cause ER stress in muscle. Finally, prolonged ER stress impairs insulin synthesis and causes pancreatic β cell apoptosis. In this review, we discuss ways in which ER stress operates as a common molecular pathway in the pathogenesis of obesity and diabetes.