The effect of physical exercise on the dynamics of glucose and insulin

Regular physical activity is indicated either to prevent and delay the onset of non-insulin-dependent diabetes or to assure a good control of diabetes by increasing insulin sensitivity and ameliorating the metabolism of glucose disappearance. Many studies and experiments have dealt with this subject.In this paper, we introduce the effect of physical activity via parameters of a mathematical model which allows us to compare the behaviour of blood glucose in normal, non-insulin-dependent diabetes and insulin-dependent diabetes people, with and without physical effort. Extreme cases of physical activity leading to hypoglycaemia or aggravating hyperglycaemia are also underlined.     

Toward Comprehensive Obesity Prevention Programs in Native American Communities

Obesity is a particularly important challenge to the health status of Native Americans. This challenge is manifest in the increasing rates of non-insulin-dependent diabetes mellitus among Native Americans. Most studies of Native American infants, preschool children, schoolchildren, and adults have confirmed a high prevalence of over weight Historical studies suggest that for many Native American communities the high rates of obesity are a relatively recent phenomenon. The specific reasons for the increase in obesity among Native Americans have not been determined, although it has been hypothesized that Native Americans have a genetic predisposition to over weight in a “westernized” environment of abundant food and decreased energy expenditure. Few detailed studies of diet or of physical activity levels of contemporary Native Americans have been published. Community-based interventions to modify diet and activity levels to prevent obesity in Native American communities are needed. Preliminary evidence from two formative school-based programs in the Southwest suggest that Native American communities are receptive to school-based interventions, and that such programs may be able to slow the rate of excess weight gain and to improve fitness in schoolchildren. Because of the cultural diversity among Native Americans, future studies should focus on collecting community- and region-specific data, and should emphasize the need for obesity prevention through culturally appropriate community-and school-based behavioral interventions.     

Genes, environment, and interactions in prevention of type 2 diabetes: a focus on physical activity and lifestyle changes

Type 2 diabetes is one of the fastest growing public health problems worldwide. Both environmental (e.g. physical activity, obesity, and diet) and genetic factors are involved in the development of type 2 diabetes. The associations between physical activity and diabetes risk have been assessed by a number of prospective studies and clinical trials. The results from these studies consistently indicate that the regular physical activity during occupation, commuting, leisure time or daily life reduces the risk of type 2 diabetes by 15-60%; and lifestyle intervention, including counselling for physical activity, nutrition, and body weight, can reduce the risk of type 2 diabetes by 40-60% among adults with impaired glucose tolerance and by about 20% among general individuals. In the past decade, studies using traditional linkage analysis and candidate-gene association approach have found dozens of genes harboring common variants that were related to the common-form type 2 diabetes. However, most reported associations are lack of reproducibility, except TCF7L2, PPARG, CAPN10, and KCNJ11. Since 2007, seven genome-wide association (GWA) studies emerged to generate a list of new diabetes genes. The genetic effects are largely of moderate size. These findings provide novel insight into the diabetes etiology and pave new avenue for predicting the disease risk using genetic information. In addition, data especially those from intervention trials display preliminary but promising evidence that the genetic variants might interact with physical activity in predisposing to type 2 diabetes. The gene-environment interactions merit extensive exploration in large, prospective studies.     

Insulin binding and insulin receptor tyrosine kinase activity are not altered in the liver of rats with non-insulin-dependent diabetes

Using the insulin-glucose clamp technique, we have previously shown that an increased sensitivity to insulin in vivo is a characteristic of the liver in rats with non-insulin-dependent diabetes induced by neonatal streptozotocin administration. We have thus studied the properties of liver insulin receptor in that model. 125I-porcine insulin binding was found normal both in isolated plasma membranes and in solubilized, wheat germ agglutinin purified receptors prepared from livers of rats with non-insulin-dependent diabetes, when compared to controls. Basal and insulin-stimulated insulin receptor kinase activities were also found normal for both the autophosphorylation of the beta subunit of the insulin receptor and the phosphorylation of the artificial substrate poly (Glu-Tyr) 4:1. Thus, in that model of chronic insulin deficiency and mild hyperglycemia: 1) liver insulin receptors are not up-regulated; 2) tyrosine kinase activity remains unaffected. This last observation supports the hypothesis that the increased insulin effect in the liver of rats with non-insulin-dependent diabetes is probably distal to the insulin receptor kinase.     

Prevalence and Secular Trends in Obesity in Pacific and Indian Ocean Island Populations

Surveys conducted in 10 Pacific island populations and in the multiethnic populations of Mauritius and Rodrigues in the Indian Ocean have provided data on the prevalence of obesity, potential etiological factors and medical hazards associated with obesity. The results indicate that the prevalence of obesity (by body mass index (BMI)) in some of these populations is among the highest in the world. Obesity related to degree of modernization is more common in urban than in rural locations and tends to be found more often in women. In two populations where longitudinal data were available, there were dramatic increases in prevalence over relatively short time periods. Obesity contributed to the risk of non-insulin-dependent diabetes mellitus (NIDDM) and was associated with other risk factors for cardiovascular disease (CVD) in all populations, but no relationship could be found with total mortality in three ethnic groups for whom data were available. A genetic susceptibility to obesity combined with social pressures that favor high energy intakes and reduced physical activity are believed to be important in these populations. The challenge for the future lies in developing culturally appropriate programs for preventing obesity and thus reducing associated morbidity, while continuing to research its behavioral and genetic determinants.     

Reduced physical activity in adults at risk for type 2 diabetes who curtail their sleep

Adults with parental history of type 2 diabetes have high metabolic morbidity, which is exacerbated by physical inactivity. Self‐reported sleep <6 h/day is associated with increased incidence of obesity and diabetes, which may be mediated in part by sleep‐loss‐related reduction in physical activity. We examined the relationship between habitual sleep curtailment and physical activity in adults with parental history of type 2 diabetes. Forty‐eight young urban adults with parental history of type 2 diabetes (27 F/21 M; mean (s.d.) age 26 (4) years; BMI 23.8 (2.5) kg/m²) each completed 13 (2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. The primary outcome of the study was the comparison of total daily activity counts between participants with habitual sleep <6 vs. ≥6 h/night. Secondary measures included daily time spent sedentary and in light, moderate, and vigorous physical activity. Short sleepers had no sleep abnormalities and showed signs of increased sleep pressure consistent with a behavioral pattern of habitual sleep curtailment. Compared to participants who slept ≥6 h/night, short sleepers had 27% fewer daily activity counts (P = 0.042), spent less time in moderate‐plus‐vigorous physical activity (?43 min/day; P = 0.010), and remained more sedentary (+69 min/day; P = 0.026). Our results indicate that young urban adults with parental history of type 2 diabetes who habitually curtail their sleep have less daily physical activity and more sedentary living, which may enhance their metabolic risk.     

The BHE rat: an animal model for the study of non-insulin-dependent diabetes mellitus

Most rodents that spontaneously develop non-insulin-dependent diabetes mellitus are obese. The exception is the BHE rat. This rat develops abnormal glucose tolerance by 300 days of age, is lipemic, has a fatty liver, and yet is not obese. The strain has existed for at least 40 years and almost 100 research papers have been published describing its metabolic characteristics and responses to diet manipulation. A subline that has a higher percentage of diabetic animals has been produced. These animals may be useful in the study of mild diabetes that exists in the absence of obesity. Berdanier, C.D. The BHE rat: an animal model for the study of non-insulin-dependent diabetes mellitus.     

A physical map of the 20q12-q13.1 region associated with type 2 diabetes

Several recent genetic studies have suggested linkage of Type 2 diabetes (non-insulin-dependent diabetes mellitus) susceptibility to a region of chromosome 20q12-q13.1. To facilitate the identification and cloning of a diabetes susceptibility gene(s) in this region, we have constructed correlated radiation hybrid and YAC/BAC contig physical maps of the region. A high-resolution radiation hybrid map encompassing 9.5 Mb between the PLC and the CEBPB genes was constructed using 68 markers: 25 polymorphic markers, 15 known genes, 21 ESTs, and 7 random genomic sequences. The physical order of the polymorphic markers within this radiation hybrid map is consistent with published genetic maps. A YAC/BAC contig that gives continuous coverage between PLC and CEBPB was also constructed. This contig was constructed from 24 YACs, 34 BACs, and 1 P1 phage clone onto which 71 markers were mapped: 23 polymorphic markers, 12 genes, 24 ESTs, and 12 random genomic sequences. The radiation hybrid map and YAC/BAC physical map enable precise mapping of newly identified transcribed sequences and polymorphic markers that will aid in linkage and linkage disequilibrium studies and facilitate identification and cloning of candidate Type 2 diabetes susceptibility genes residing in 20q12-q13.1.     

Chlorpropamide-alcohol flushing: a dominantly inherited trait associated with diabetes.

A simple test was devised to identify people susceptible to chlorpropamide-alcohol flushing (CPAF). Subjects were given a placebo tablet, followed by sherry 12 and 36 hours later. They then received a chlorpropamide tablet and sherry again after 12 and 36 hours. This single-dose challenge test was given to non-insulin-dependent diabetics, insulin-dependent diabetics, and normal subjects. CPAF was common in the non-insulin-dependent diabetics but rare in the other groups. When the test was used in identical twins and families of affected subjects CPAF appeared to be a dominantly inherited trait. We conclude that facial flushing after alcohol in people taking chlorpropamide is related to non-insulin-dependent diabetes, especially when there is a strong family history of diabetes, but not to insulin-dependent diabetes. It is a dominantly inherited trait.     

Selected indicators of calcium-phosphate metabolism in patients with diabetes mellitus

The changes in blood serum concentrations of calcium, magnesium, inorganic phosphate, total activity of alkaline phosphatase and the activity of its bone fraction, as well as urinary excretion of calcium, phosphate, hydroxyproline and oxalate have been measured in 31 patients with insulin-dependent (type I) diabetes, in 31 patients with non-insulin-dependent (type II) diabetes and in 29 healthy subjects in the condition of low-calcium diet. The elevated urinary excretion of calcium, phosphate, hydroxyproline and oxalate, lowered blood serum level of magnesium, and increased total and bone fraction activities of alkaline phosphatase were found in diabetic patients. The urinary excretion of calcium and hydroxyproline, and the activity of bone fraction alkaline phosphatase were significantly higher in patients with type II diabetes than in those with type I diabetes. It was concluded that there is a significant relation between the state of metabolic normalization of diabetes and the degree of biochemical aberrations concerning calcium-phosphate metabolism.     

Inhibitors can arrest the membrane activity of human islet amyloid polypeptide independently of amyloid formation.

Human islet amyloid polypeptide (hIAPP), co-secreted with insulin from pancreatic beta cells, misfolds to form amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). Like many amyloidogenic proteins, hIAPP is membrane-active: this may be significant in the pathogenesis of NIDDM. Non-fibrillar hIAPP induces electrical and physical breakdown in planar lipid bilayers, and IAPP inserts spontaneously into lipid monolayers, markedly increasing their surface area and producing Brewster angle microscopy reflectance changes. Congo red inhibits these activities, and they are completely arrested by rifampicin, despite continued amyloid formation. Our results support the idea that non-fibrillar IAPP is membrane-active, and may have implications for therapy and for structural studies of membrane-active amyloid.     

The modern concept of the regulatory role of peptides of the glyproline family in the correction of hemostasis system function during development of diabetes mellitus

The experimental data on the therapeutic and prophylactic antidiabetogenic effect of di-, tri-, and tetrapeptides of the glyproline family with the additional inclusion of arginine or leucine at different positions are presented. The results are obtained using two animal models: with insulin-dependent diabetes mellitus (type 1), and persistent hyperglycemia similar to development of non-insulin-dependent diabetes mellitus (type 2) in humans. It is shown that repeated intranasal administration of Pro-Gly, Pro-Gly-Pro, Pro-Gly-Pro-Arg, Pro-Gly-Arg, Arg-Pro-Gly, Arg-Pro-Gly-Pro, Gly-Pro-Arg, Pro-Arg-Gly, Pro-Gly-Pro-Leu, Leu-Pro-Gly-Pro peptides to rats with hyperglycemia of different etiology led to the combined normoglycemic and anticoagulant effects in the blood plasma. The concept of the regulatory role of short proline-containing peptides, involving the universality of their action in the organism and directed towards the regulation of both hemostasis and insular systems in a variety of their physiological and clinical manifestations, was formulated.     

Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin-dependent diabetes.

The single-challenge test for chlorpropamide-alcohol flushing (CPAF) was used to study two groups of patients with non-insulin-dependent diabetes and a family history of the disease who were distinguished only by their age at diagnosis (under and over 30). Their relatives were also studied. The proportions of patients showing CPAF in both groups were similar, and the family histories suggested dominant inheritance. When offspring of diabetics in whom the disease was diagnosed early were studied CPAF seemed to precede the appearance of diabetes. We conclude that the patients in both groups had the same, distinct syndrome, which is characterised by diabetes diagnosed at any age that is inherited as an autosomal dominant trait and associated with CPAF. This syndrome, which constitutes about one-fifth of all cases of non-insulin-dependent diabetes, may be detected with a single-challenge CPAF test before the onset of glucose intolerance. CPAF therefore acts as a genetic marker for the syndrome.     

Signal transduction crosstalk in the endocrine system: pancreatic beta-cells and the glucose competence concept.

Crosstalk between intracellular signalling systems is recognized as the principal means by which a cell orchestrates coordinate responses to stimulation by neurotransmitters, hormones or growth factors. The functional consequences of crosstalk are evident at multiple levels within a given signalling cascade, including the regulation of receptor-ligand interactions, guanine nucleotide-binding proteins, enzyme activities, ion channel function and gene expression. Here we focus on the pancreatic beta-cells of the islets of Langerhans to illustrate the important role crosstalk plays in the regulation of glucose-induced insulin secretion. Recent studies indicating a synergistic interaction in beta-cells between the glucose-regulated ATP-dependent signalling system and the hormonally regulated cAMP-dependent signalling system are emphasized. This interaction gives beta-cells the ability to match the ambient concentration of glucose to an appropriate insulin secretory response, a process we refer to as the induction of glucose competence. The glucose competence concept may provide new insights into the etiology and treatment of non-insulin-dependent diabetes mellitus (Type II diabetes).     

Potential role of N-myristoyltransferase in pathogenic conditions

N-Myristoyltransferase (NMT) is the enzyme that catalyzes the covalent transfer of myristic acid to the N-terminal glycine residue of a protein substrate. In this review article, I summarize that NMT may have a potential role in cardiac muscle in the experimentally induced ischemia-reperfusion rat model and also in the streptozotoein-induced diabetic rat. Both the expression and activity of NMT were increased by ischemia-reperfusion. Immunohistochemical studies showed cytosolic localization of NMT in normal rat heart and predominant nuclear localization after ischemia followed by reperfusion. However, the localization of NMT is reversed by treatment with a calpain inhibitor (ALLM N-Ac-Leu-Leu-methioninal). During ischemia-reperfusion, the degradation of c-Src, which is a substrate of NMT, was observed. These findings suggested that the Src signaling may be impaired in ischemia-reperfusion owing to the altered localization of NMT from cytoplasm to nucleus. Streptozotocin-induced diabetes (an animal model for insulin-dependent diabetes mellitus) resulted in a 2.0-fold increase in rat liver NMT activity as compared with control animals. In obese (fa/fa) Zucker rats (an animal model for non-insulin-dependent diabetes mellitus), there was an approximately 4.7-fold lower liver particulate NMT activity as compared with control lean rat livers. Administration of sodium orthovanadate to the diabetic rats normalized liver NMT activity. These results would indicate that rat liver particulate NMT activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation. These are the first studies demonstrating the role of NMT in the pathogenesis of ischemia-reperfusion and diabetes mellitus. These conditions remain an important area of investigation.     

Impaired FAD-glycerophosphate dehydrogenase activity in islet and liver homogenates of fa/fa rats

The mitochondrial FAD-linked enzyme glycerophosphate dehydrogenase plays a key role in the pancreatic B-cell glucose sensing device. In the present study, the activity of this enzyme was examined in islets of fa/fa rats in which inherited diabetes mellitus is associated with obesity, hyperinsulinism and severe insulin resistance. The specific activity of both FAD-linked glycerophosphate dehydrogenase and glutamate dehydrogenase were decreased in islet and liver homogenates prepared from fa/fa, as compared to Fa/Fa, rats, this coinciding with a low ratio between glutamateoxalacetate and glutamate-pyruvate transaminase activity in both islet and liver extracts, islet hyperplasia, hyperinsulinemia and hepatic steatosis in the hyperglycemic fa/fa rats. It is speculated that a low activity of FAD-linked glycerophosphate dehydrogenase in the pancreatic B-cell may participate to the perturbation of glucose homeostasis in fa/fa rats, like in other animal models of non-insulin-dependent diabetes mellitus.     

Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus.

Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin-dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin-dependent diabetes mellitus showed a significant improvement in their glucose tolerance, which paralleled the severity of their diabetes. This response seems to reflect decreased degradation of insulin rather than increased pancreatic output. These observations suggest that treatment with chloroquine or suitable analogues may be a new approach to the management of diabetes.     

Reductions in cortical activity during priming

Priming is a nonconscious form of memory in which an encounter with a stimulus influences the subsequent identification, production or classification of the same or a related stimulus. Neuroimaging studies have revealed that behavioral priming is typically accompanied by reduced activity in several cortical regions. We review recent studies that have concerned two key issues. First, specificity effects produced by changes between study and test in either the physical features of stimuli or the behavioral response reveal cortical sensitivity to the perceptual, conceptual and stimulus-to-decision mapping properties of primed items. Second, correlations between behavioral priming and activity reductions are robust across a range of tasks and procedures in prefrontal regions but not in posterior regions. On the basis of these recent studies, we suggest that the reduction in cortical activity during priming involves at least two different mechanisms.     

Glucose-induced insulin mRNA accumulation is impaired in islets from neonatal streptozotocin-treated rats.

According to the glucose toxicity hypothesis, hyperglycemia contributes to defective beta-cell function in type 2, non-insulin-dependent diabetes mellitus. This concept is supported by substantial data in rodent models of diabetes. However, the ability of glucose to stimulate the accumulation of insulin mRNA, a critical feature of normal beta-cell physiology, has not been investigated in in vivo models of chronic hyperglycemia. The aim of this study was to determine whether glucose-induced insulin mRNA accumulation is impaired in the neonatal streptozotocin-treated rat (n0-STZ rat), a model of non-obese, non-insulin-dependent diabetes mellitus. Islets of Langerhans isolated from n0-STZ and control rats were cultured for 24 h in the presence of 2.8 or 16.7 mmol/L glucose, and insulin mRNA levels were measured by Northern analysis. Insulin mRNA levels were increased more than twofold by glucose in control islets. In contrast, no significant effect of glucose was found on insulin mRNA levels in n0-STZ islets. We conclude that insulin gene regulation by glucose is impaired in n0-STZ rat islets.     

Diabetes mellitus in Mohawks of Kahnawake,PQ: a clinical and epidemiologic description.

The authors report the rates of obesity, hypertension, hypercholesterolemia, smoking, and macrovascular and microvascular complications among Mohawks of Kahnawake, PQ, who have non-insulin-dependent diabetes mellitus. The data were derived from a study comparing rates of macrovascular and microvascular complications among the diabetic subjects and a nondiabetic group matched for age and sex. The data for both groups were collected by means of chart review, interview and body measurement. There were no important differences between the male and female diabetic subjects. Both sexes had high levels of obesity, hypertension, hypercholesterolemia and diabetic complications. A total of 86% of the diabetic subjects were obese; the rate was also very high (74%) among the nondiabetic subjects. The mean age at onset of diabetes, 59 years, was 10 years higher than that observed in Oneida Iroquois of Ontario. The rates of macrovascular disease among the diabetic subjects were higher than those found among Cree/Ojibwa in Ontario and Manitoba. Our findings add to the knowledge of non-insulin-dependent diabetes in North American Indians in Canada and show that there are differences between our Mohawk subjects and diabetic people of other native communities.