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This study examined the validity of the Klonoff and Landrine Illness-Belief Scale when applied to Latino college students (n = 156; 34% male, 66% female) at high risk for future diabetes onset. Principal factor analysis yielded four significant factors--emotional, folk beliefs, punitive, gene/hereditary--which accounted for 64.5% of variance and provided a culturally relevant Latino perspective of the causes of diabetes. Additional analyses by age, gender, immigrant status, and psychological acculturation revealed significant differences by age on the emotional and folk illness factors and a negative correlation between assimilation and endorsement of the emotional factor. The implication of these four illness factors for predicting health-related behaviors and health outcomes among young Latinos was discussed as were recommendations for future research. Keywords: health; diabetes; Latinos; cultural illness beliefs; college students

A study was conducted to evaluate the age where one can determine the increased risk of development of cardiovascular disease and diabetes in adulthood and the relationship between first-year weight gain and increased risk. Results indicated that rapid weight gain increased the risk of developing cardiovascular disease and diabetes during adulthood.

Several studies are conducted to show that the mutations in C2orf37 lead to hypogonadism, alopecia, diabetes mellitus, mental retardation and extrapyramidal syndrome (Woodhouse-Sakati syndrome) in humans. The disorder is shown to be a rare autosomal recessive multisystemic disorder, caused by the encoding of a nucleolar protein by the mutations.

The study evaluates the association between serum fetuin-A levels and incident diabetes mellitus in older persons. Evidence suggests serum fetuin-A is associated with incident diabetes in well-functioning older persons, independent of other insulin resistance markers.

We undertook a longitudinal qualitative study involving of 20 patients from Scotland who had type 2 diabetes. We looked at their perceptions and understandings of why they had developed diabetes and how, and why, their causation accounts had changed or remained stable over time. Respondents, all of whom were white, were interviewed four times over a 4-year period (at baseline. 6, 12 and 48 months). Their causation accounts often shifted, sometimes subtly, sometimes radically, over the 4 years. The experiential dimensions of living with, observing, and managing their disease over time were central to understanding the continuities and changes we observed. We also highlight how, through a process of removing, adding and/or de-emphasising explanatory factors, causation accounts could be used as 'resources' to justify or enable present treatment choices. We use our work to support critiques of social cognition theories, with their emphasis upon beliefs being antecedent to behaviours. We also provide reflections upon the implications of our findings for qualitative research designs and sampling strategies. Keywords: Type 2 diabetes Patients' perceptions Disease accounts Research design UK Scotland

Effect of stimulation of glucokinase (GK) export from the nucleus by small amounts of sorbitol on hepatic glucose flux in response to elevated plasma glucose was examined in 6-h fasted Zucker diabetic fatty rats at 10 wk of age. Under basal conditions, plasma glucose, insulin, and glucagon were ~8 mM, 2,000 pmol/l, and 60 rig/l, respectively. Endogenous glucose production (EGP) was 44 [+ or -] 4 [micro]mol*[kg.sup.-l]*[min.sup.-1]. When plasma glucose was raised to ~17 raM, GK was still predominantly localized with its inhibitory protein in the nucleus. EGP was not suppressed. When sorbitol was infused at 5.6 and 16.7 [micro]mol*[kg.sup.-l]*[min.sup.-1], along with the increase in plasma glucose, GK was exported to the cytoplasm. EGP (23 [+ or -] 19 and 12 [+ or -] 5 [micro]mol*[kg.sup.-1]*[min.sup.-1]) was suppressed without a decrease in glucose 6-phosphatase flux (145 [+ or -] 23 and 126 [+ or -] 16 vs. 122 [+ or -] 10 [micro]mol*[kg.sup.-l]*[min.sup.-1] without sorbitol) but increased in glucose phosphorylation as indicated by increases in glucose recycling (122 [+ or -] 17 and 114 [+ or -] 19 vs. 71 [+ or -] 11 [micro]mol*[kg.sup.-l]*[min.sup.-1]), glucose-6-phosphate content (254 [+ or -] 32 and 260 [+ or -] 35 vs. 188 [+ or -] 20 nmol/g liver), fractional contribution of plasma glucose to uridine 5'-diphosphateglucose flux (43 [+ or -] 8 and 42 [+ or -] 8 vs. 27 [+ or -] 6%), and glycogen synthesis from plasma glucose (20 [+ or -] 4 and 22 [+ or -] 5 vs. 9 [+ or -] 4 [micro]mol glucose/g liver). The decreased glucose effectiveness to suppress EGP and stimulate hepatic glucose uptake may result from failure of the sugar to activate GK by stimulating the translocation of the enzyme. obese-type 2 diabetes; glucokinase regulatory protein

The search for target analytes to uncover the misuse of long acting insulin analogues (Lantus, Insulin Glargine; Levemir, Insulin Detemir) in doping control samples led to the identification of several degradation products of insulin or its synthetic analogues. Specimens obtained from healthy volunteers or patients and athletes suffering from diabetes mellitus contained DesB30, DesB24-30, and DesB25-30 human insulin or DesB30-32, DesB31-32, and DesB24-32 Lantus, respectively. Analytes were purified from urine by immunoaffinity chromatography 0AC) with subsequent liquid chromatography--tandem mass spectrometry analysis. The employed analytical procedure was validated for qualitative determination considering the main metabolic products DesB30 human insulin and DesB30-32 Lantus. The occurrence of the identified Lantus degradation products in urine provided the direct and unambiguous evidence for an administration of this insulin analogue. For the determination of surreptitious Levemir or recombinant human insulin applications, an unequivocal argument was not detected, but promising approaches based on a modified insulin degradation profile with altered relative intensities of metabolites are presented.

Two recent studies have shown that the glucose intolerance and impaired insulin secretion of the C57BL/6J mouse strain results from oxidative stress due to a mutated nicotinamide nucleotide transhydrogenase. Reproduction of this phenotype, by mutating the same enzyme in another strain with normal glucose tolerance, suggests that the mechanism of the transhydrogenase-dependent inhibition of insulin secretion involves a partial uncoupling by the UCP2 protein. These exciting findings raise important questions, not least their potential relevance for human diabetes.

The insulin-regulated glucose transporter GLUT4 is a key modulator of whole body glucose homeostasis, and its selective loss in adipose tissue or skeletal muscle causes insulin resistance and diabetes. Here we report an RNA interference-based screen of protein kinases expressed in adipocytes and identify four negative regulators of insulin-responsive glucose transport: the protein kinases PCTAIRE-1 (PCTK1), PFTAIRE-1 (PFTK1), I[kappa]B kinase [alpha], and MAP4K4/NIK. Integrin-linked protein kinase was identified as a positive regulator of this process. We characterized one of these hits, MAP4K4/NIK, and found that it is unique among mitogen-activated protein (MAP) kinases expressed in cultured adipocytes in attenuating hexose transport. Remarkably, MAP4K4/NIK suppresses expression of the adipogenic transcription factors C/EBP[alpha], C/EBP[beta], and PPAR[gamma], and of GLUT4 itself in these cells. RNA interference-mediated depletion of MAP4K4/NIK early in differentiation enhances adipogenesis and triglyceride deposition, and even in fully differentiated adipocytes its loss up-regulates GLUT4. Conversely, conditions that inhibit adipogenesis such as TNF-[alpha] treatment or depletion of PPAR[gamma] markedly up-regulate MAP4K4/ NIK expression in cultured adipocytes. Furthermore, TNF-[alpha] signaling to down-regulate GLUT4 is impaired in the absence of MAP4K4/NIK, indicating that MAP4K4 expression is required for optimal TNF-[alpha] action. These results reveal a MAP4K4/NIK-dependent signaling pathway that potently inhibits PPAR3,-responsive gene expression, adipogenesis, and insulin-stimulated glucose transport. GLUT4 function | adipocyte differentiation | protein kinase screening

Estrogen is known to influence glucose homeostasis with dominant effects in the liver, but the role of estrogen receptors in muscle glucose metabolism is unknown. In the present study, we investigated the expression of the two estrogen receptors, ER[beta] and ER[alpha], and their influence on regulation of the glucose transporter, GLUT4, and its associated structural protein, caveolin-1, in mouse gastrocnemius muscle. Immunohistochemical analysis revealed that ER[alpha] and ER[beta] are coexpressed in the nuclei of most muscle cells, and that their levels were not affected by absence of estradiol [in aromatase-knockout (ArKO) mice]. GLUT4 expression on the muscle cell membrane was not affected by loss of ER[beta] but was extremely reduced in ER[[alpha].sup.-/-] mice and elevated in ArKO mice. RT-PCR confirmed a parallel reduction in GLUT4 mRNA levels in ER[[alpha].sup.-/-] mice. Upon treatment of ArKO mice with the ER[beta] agonist 2,3-bis(4-hydroxyphenyl)propionitrile, GLUT4 expression was reduced. By immunofluorescence and Western blotting, caveolin-1 expression was higher in ArKO mice and lower in ER[[beta].sup.-/-] and ER[[alpha].sup.-/-] mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ER[[beta].sup.-/-] and ER[[alpha].sup.-/-] mice. These results reveal that ER[alpha] is a positive regulator of GLUT4 expression, whereas ER[beta] has a suppressive role. Both ER[beta] and ER[alpha] are necessary for optimal caveolin-1 expression. Taken together, these results indicate that colocalization of caveolin-1 and GLUT4 is not an absolute requirement for muscle glucose metabolism but that reduction in GLUT4 could be contributing to the insulin resistance observed in ER[[alpha].sup.-/-] mice. caveolin-1 | diabetes | aromatase

Introduction: This paper compares the prevalence estimates of diabetes and cardiovascular disease (CVD) risk factors in the Indigenous and non-Indigenous New South Wales (NSW) prisoner population in 1996 and 2001, and also compares the 2001 prevalence estimates with Australian population data. Methods: In 1996 and 2001,789 and 916 prisoners, respectively, in NSW underwent a face-to-face interview covering behavioural risks and physical and mental health. Weight, height and blood pressure were recorded and blood was taken for measurement of cholesterol and random blood sugar. Results: The prevalence of hypertension, hypercholesterolaemia and smoking were lower in the 2001 prison survey as compared with the 1996 survey but the prevalence of smoking was extremely high in both the prison surveys (88% in 1996 and 79% in 2001). There were no differences in the age and sex-adjusted prevalence estimates for any condition except that the prison sample had a higher standardised morbidity ratio for angina than the AusDiab population. Conclusion: This study highlights the high prevalence of CVD risk factors, particularly in younger prisoners, when compared with the Australian non-prison population. Implications: Programs should be put in place to routinely screen for chronic disease conditions and to educate Australian prisoners regarding CVD and diabetes risk factors and their long-term management. (Aust N Z J Public Health 2005; 29:318-23)

Insulin and IGF-I activate antiapoptotic pathways via insulin receptor substrate (IRS) proteins in most mammalian cells, including [beta]-cells. IRS-I knockout (IRS-1KO) mice show growth retardation, hyperinsulinemia, and hyperplastic but dysfunctional islets without developing overt diabetes, whereas IRS-2KOs develop insulin resistance and islet hypoplasia leading to diabetes. Because both models display insulin resistance, it is difficult to differentiate islet response to insulin resistance from islet defects due to loss of proteins in the islets themselves. We used a transplantation approach, as a means of separating host insulin resistance from islet function, to examine alterations in proteins in insulin/IGF-I signaling pathways that may contribute to [beta]-cell proliferation and/or apoptosis in IRS-1KO islets. Islets isolated from wild-type (WT) or IRS-1KO mice were transplanted into WT or insulin-resistant IRS-1KO males under the kidney capsule. The [beta]-cell mitotic rate in transplanted islets in IRS-1KO recipients was increased 1.5-fold compared with WT recipients and was similar to that in endogenous pancreases of IRS-1KOs, whereas [beta]-cell apoptosis was reduced by ~80% in IRS-1KO grafts in IRS-1KO recipients compared with WT recipients. Immunohistochemistry showed a substantial increase in IRS-2 expression in IRS-1KO islets transplanted into IRS-1KO mice as well as in endogenous islets from IRS-1KOs. Furthermore, enhanced cytosolic forkhead transcription factor (FoxO1) staining in IRS-1KO grafts suggests intact Akt/PKB activity. Together, these data indicate that, even in the absence of insulin resistance, [beta]-cells deficient in IRS-1 exhibit a compensatory increase in IRS-2, which is associated with islet growth and is characterized by both proliferative and antiapoptotic effects that likely occur via an insulin/IGF-I/IRS-2 pathway. insulin receptor substrate proteins; islets; transplantation; insulin resistance; [beta]-cell growth

Calpains are CA(super 2+)-dependent cysteine proteases that modulate cellular function. The findings on the role of the calpain superfamily in various disorders like diabetes, cataracts, multiple sclerosis, cancer and Duchenne's muscular dystrophy, focusing on limb-girdle muscular dystrophy type 2A, the most extensively characterized human calpainopathy are reviewed.

Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7-22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60-68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml x [kg.sup.-1] x [min.sup.-1] with plasma samples taken before and at three 40-rain intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were ~20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus. fetal alcohol syndrome; vasopressin; plasma osmolality; thirst; vasopressin messenger ribonucleic acid; neurohypophysis

The effect of fat distribution on disease risk is a subject of great interest. Central fat has been measured anthropometrically, by computed tomography, and by magnetic resonance imaging. Both cross-sectional and longitudinal studies have related central fat to type 2 diabetes mellitus and cardiovascular disease, independent of body mass index. The mechanism may relate to increased lipolysis causing the fiver to increase glucose and very low density lipoprotein output, while muscle uses less. This leads to a rise in blood glucose and triglycerides, a drop in HDL cholesterol, and an increase in small, dense LDL particles. There is also an increase in blood pressure and inflammatory markers. Certain populations put on excess fat more centrally than others. These include Asian populations. It is likely that with better differentiation of abdominal fat into visceral and subcutaneous depots, clearer data will accrue on their impact on disease risk. Key words: central fat, diabetes, cardiovascular disease

The properties of two paralogs of the coactivator DCoH were compared to analyze the idea that they fulfill distinct functional roles that may account for the phenotypes of DCoH1 knockout mice. Results demonstrate that DCoH2 mediates the same enzymatic and coactivator activities as DCoH1 but with different surface residues and different requirements for binding HNF1alpha in vitro.

Sleep deprivation and sleep disorders are believed to be the causative factors in diabetes and obesity that leads to sleep disordered breathing (SDB). The two-day meeting by National Center on Sleep Disorders Research aimed to boost recognition and treatment of sleep disorders while various action plans were suggested to improve the quality of life.

The study conducted to find out the causes of neonatal diabetes is presented. The study reveals that Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and can also be associated with muscle weakness and epilepsy.

Diabetes mellitus is a significant public health threat in the United States, fueled by some unfortunate population trends--including the rise in obesity, which has more than doubled in the last […]

Gangliosides are sialic acid-containing glycosphingolipids that are present on all mammalian plasma membranes where they participate in recognition and signaling activities. We have established mutant mice that lack GM3 synthase (CMP-NeuAc:lactosylceramide [alpha]2,3-sialyltransferase; EC 2.4.99.-). These mutant mice were unable to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid. The mutant mice were viable and appeared without major abnormalities but showed a heightened sensitivity to insulin. A basis for the increased insulin sensitivity in the mutant mice was found to be enhanced insulin receptor phosphorylation in skeletal muscle. Importantly, the mutant mice were protected from high-fat diet-induced insulin resistance. Our results show that GM3 ganglioside is a negative regulator of insulin signaling, making it a potential therapeutic target in type 2 diabetes.

The mammalian securin, pituitary tumor transforming gene (PTTG), regulates sister chromatid separation during mitosis. Mice or cell lines deficient in PTTG expression, however, are surprisingly viable. Here we show that PTTG disruption in mice (PTTG-/-) severely impairs glucose homeostasis leading to diabetes during late adulthood, especially in males associated with nonautoimmune insulinopenia and reversed alpha/beta cell ratio. Islet beta cell mass in PTTG-/- mice was already diminished before development of frank diabetes and only increased minimally during growth. BrdUrd incorporation of islet cells in PTTG-null mice was [approximately equal to] 65% lower (P < 0.005) than in the WT pancreas, whereas apoptosis rates were similar. PTTG-/- beta cells had pleiotropic nuclei, suggesting defects in cell division. The results indicated that securin is indispensable for normal pancreatic beta cell proliferation.

In normoglycemic offspring of two type 2 diabetic parents, low insulin sensitivity ([S.sub.I]) and low insulin-independent glucose effectiveness ([S.sub.G]) predict the development of diabetes one to two decades later. To determine whether low [S.sub.I], low [S.sub.G], or low acute insulin response to glucose are predictive of diabetes in a population at low genetic risk for disease, 181 normoglycemic individuals with no family history of diabetes (FH-) and 150 normoglycemic offspring of two type 2 diabetic parents (FH+) underwent i.v. glucose tolerance testing (IVGTT) between the years 1964-82. During 25 [+ or -] 6 years follow-up, comprising 2,758 person years, the FH- cohort (54 [+ or -] 9 years) had an age-adjusted incidence rate of type 2 diabetes of 1.8 per 1,000 person years, similar to that in other population-based studies, but significantly lower than 16.7 for the FH+ cohort. Even when the two study populations were subdivided by initial values of [S.sub.I] and [S.sub.G] derived from IVGTT's performed at study entry, there was a 10- to 20-fold difference in age-adjusted incidence rates for diabetes in the FH- vs. FH+ individuals with low [S.sub.I] and low [S.sub.G]. The acute insulin response to glucose was not predictive of the development of diabetes when considered independently or when assessed as a function of [S.sub.I], i.e., the glucose disposition index. These data demonstrate that low glucose disposal rates are robustly associated with the development of diabetes in the FH+ individuals, but insulin resistance per se is not sufficient for the development of diabetes in individuals without family history of disease and strongly suggest a familial factor, not detectable in our current measures of the dynamic responses of glucose or insulin to an IVGTT is an important risk factor for type 2 diabetes. Low [S.sub.I] and low [S.sub.G], both measures of glucose disposal, interact with this putative familial factor to result in a high risk of type 2 diabetes in the FH+ individuals, but not in the FH- individuals.

The enzyme 11[beta] hydroxysteroid dehydrogenase-1 (11[beta] HSD-1) regenerates active glucocorticoids from inactive glucocorticoids. When over-expressed in adipose tissue, this enzyme was shown to promote increased visceral adipose levels. The resulting visceral obesity was associated with insulin-resistant diabetes and dyslipidemia. Increased adipocyte 11[beta] HSD-1 is a possible cause of visceral obesity in humans. Key Words: obesity, 11[beta] hydroxysteroid dehydrogenase, adipocytes, glucocorticoids, metabolic syndrome, diabetes, dyslipidemia

Defects in pancreatic [beta]-cell function contribute to the development of type 2 diabetes, a polygenic disease that is characterized by insulin resistance and compromised insulin secretion. Hepatocyte nuclear factors (HNFs) -1[alpha], -3[beta], -4[alpha], and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in [beta]-cell development and function. In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1[[alpha].sup.+/-], Hnf-3[[beta].sup.+/-], or Hnf-4[[alpha].sup.+/-], causes impaired glucose-stimulated insulin secretion in mice. To investigate the possible functional relationships between these transcription factors on [beta]-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-[1.sup.+/-]/Hnf-1[[alpha].sup.+/-], Pdx-[1.sup.+/-]/Hnf-3[[beta].sup.+/-], Pdx-[1.sup.+/-]/Hnf-4[[alpha].sup.+/-, Hnf-1[[alpha].sup.+/-]/Hnf-4[[alpha].sup.+/-], and Hnf-3[[beta].sup.+/-]/Hnf-4[[alpha].sup.+/-]. The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1[alpha](Pdx-[1.sup.+/-]/Hnf-1[[alpha].sup.+/-]), or Pdx-1 and Hnf-3[beta](Pdx-[1.sup.+/-]/Hnf-3[[beta].sup.+/-]). Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-[1.sup.+/-] mice alone. The loss in [beta]-cell function in Pdx-[1.sup.+/-]/Hnf-3[[beta].sup.+/-] mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-[1.sup.+/-]/Hnf-1[[alpha].sup.+/-] mice. The islet cell architecture was also abnormal in Pdx-[1.sup.+/-]/Hnf-3[[beta].sup.+/-] and Pdx-[1.sup.+/-]/Hnf-1[[alpha].sup.+/-] mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. Our data suggest that functional interactions between key islet regulatory factors play an important role in maintaining islet architecture and [beta]-cell function. These studies also established polygenic mouse models for investigating the mechanisms contributing to [beta]-cell dysfunction in diabetes. hepatocyte nuclear factors | diabetes mellitus | insulin secretion | pancreatic islets

In nonobese diabetic (NOD) mice, the autoimmune attack of the [beta]-cells in pancreatic islets is now believed to result from abnormal thymic selection. Accordingly, grafts of thymic epithelium from NOD donors to athymic recipients promote autoimmune islet inflammation in normal strains, and intrathymic islet grafts decrease the incidence of disease in NOD animals. Two competing hypotheses of abnormal thymic selection in diabetic mice have been proposed: deficient negative selection with poor elimination of aggressive organ-specific T cells vs. deficient positive selection of protective T regulatory cells. We have now addressed these alternatives by grafting, into young NOD mice whose own thymus was left intact, newborn NOD thymuses containing allogeneic pancreatic islets. If the NOD defect represented poor negative selection, these animals would develop disease at control rates, as the generation of autoreactive T cells proceeds undisturbed in the autologous thymus. In contrast, if NOD thymuses are defective in the production of T regulatory cells, lower disease incidence is expected in the chimeras, as more protective cells can be produced in the grafted thymus. The results show a reduced incidence of diabetes in the chimeras (24%) as compared with control (72%) NOD mice, throughout adult life. We conclude that amelioration of NOD mice by intrathymic islet grafts is not caused by enhanced negative selection and suggest that autoimmune diabetes in this system is the result of inefficient generation of T regulatory cells in the thymus.

Research into the rates of binge eating disorder and other psychopathology in type II diabetes mellitus is presented. It was found that binge eating disorder was present in around 25% of patients with type II diabetes mellitus surveyed. However, it is uncertain whether the rates of binge eating disorder are connected only with body mass index.

Research has been conducted on the retinoids identified as RXR agonists for the treatment of non-insulin-dependent diabetes mellitus. The highly convergent synthesis of these retinoids has been performed and described.

Research has been conducted on the aldose reductase (AR), a NADPH-dependent enzyme causing diabetic complications. The results of the interactions of R- and S-isomers with AR under physiological conditions in the attempt to elucidate the inhibition modes are discussed.

Medical scientists describe two newborn babies who developed diabetes because they had a complete absence of the enzyme glucokinase. This enzyme regulates the secretion of insulin in response to glucose ingestion.

Research has been conducted on the glucagon-like peptide-1. The role of this peptide in diabetes treatment has been investigated.

A study in mice shows that decreased sensitivity of beta cell K(sub ATP) channels to ATP/ADP can cause diabetes. Increased ATP/ADP levels resulting from glucose metabolism stimulate the channel to close, which in turn triggers insulin secretion.

Some 130 patients with a past history of abuse were surveyed to study whether child and domestic abuse could contribute to the likelihood of developing diabetes. Since child and domestic abuse were found to be chronic stressors, the study concluded that past victimization may make former victims of abuse more susceptible to diabetes or to its symptoms than nonabused individuals. The study further suggests that past victimization could likewise lead to a host of other health problems.

Streptozotocin (STZ) selectively destroys insulin-producing beta islet cells of the pancreas providing a model of type I diabetes. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme whose overactivation by DNA strand breaks depletes its substrate [NAD.sup.+] and then ATP, leading to cellular death from energy depletion. We demonstrate DNA damage and a major activation of PARP in pancreatic islets of STZ-treated mice. These mice display a 500% increase in blood glucose and major pancreatic islet damage. In mice with homozygous targeted deletion of PARP (PARP -/-), blood glucose and pancreatic islet structure are normal, indicating virtually total protection from STZ diabetes. Partial protection occurs in PARP +/- animals. Thus, PARP activation may participate in the pathophysiology of type I diabetes, for which PARP inhibitors might afford therapeutic benefit.

Rats treated with varying doses of streptozotocin (STZ) were used to investigate the relationships among postabsorptive glucose concentration, hepatic glucose output and glucose clearance. Results reveal that the pathophysiology of STZ-induced diabetes in rats involves primarily reduced glucose clearance although there is a contribution from the hepatic glucose output in experimental animals receiving the highest dose of STZ.