Insulin resistance is a hallmark of type 2 diabetes, and many insights into the functions of insulin have been gained through the study of mice lacking the IR. To gain a better understanding of the role of insulin action in the brain versus peripheral tissues, we created 2 mouse models ...

Mushrooms are low calorie food with very little fat and are highly suitable for obese persons. With no starch and very low sugars, they are the 'delight of the diabetics'. Combination of herbal drugs (or isolated phytochemicals) is found to be beneficial in certain diseases when given along with conventional ...

OBJECTIVE: Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE(-/-) model of accelerated atherosclerosis. RESEARCH DESIGN AND METHODS: ApoE(-/-) ...

Hypoalgesia is one of the serious complications in diabetes. Since there are few therapeutic treatments for this diabetic hypoalgesia, the present study was designed to examine the effect of acetyl-L-carnitine (ALC) on the changes of nociceptive threshold in diabetic mice. For prophylactic study, ALC was administered once daily from 1 ...

Taguchi et al. (Reports, 20 July 2007, p. 369) reported that mice heterozygous for a null mutation in insulin receptor substrate-2 (Irs2) display a 17% increase in median life span. However, using the same mouse model, we find no evidence for life-span extension and suggest that the findings of Taguchi ...

Excess oxygen radical formation is suggested to be involved in the etiology of diabetic embryopathy. We aimed to investigate the effects of altered maternal antioxidative status in conjunction with a varied severity of the maternal diabetic state on embryonic development by using mice with different gene expression of CuZn superoxide ...

AIMS/HYPOTHESIS: Diabetic patients are at increased risk of cardiomyopathy, acute myocardial infarction and loss of cardiac progenitor cells (CPCs), but the aetiology is poorly understood. We hypothesised a significant role for mannose-binding lectin (MBL) in cardiomyopathies associated with hyperglycaemia. METHODS: The role of MBL in myocardial ischaemia and reperfusion (MI/R) ...

INTRODUCTION: Brickellia veronicifolia (Kunth) Gray (Asteraceae) (BV) is broadly commercialized for treating gastrointestinal diseases (stomach aches, biliary colics and dyspepsia), arthritis, diabetes and painful inflammatory complaints. AIMS OF THE STUDY: In order to complete the preclinical pharmacological profile of BV, first the antinociceptive effect of an organic extract (BVE) and ...

OBJECTIVE: Acute activation of G protein-coupled receptor 40 (GPR40) by free fatty acids (FFAs) or synthetic GPR40 agonists enhances insulin secretion. However, it is still a matter of debate whether activation of GPR40 would be beneficial for the treatment of type 2 diabetes, since chronic exposure to FFAs impairs islet ...

Glucose tolerance progressively declines with age in humans and is often accompanied by insulin resistance and a high prevalence of type 2 diabetes. Little is known about the mechanism underlying the age-related changes in glucose metabolism. Here we reported that acid-sensing ion channel 3 (ASIC3) is functionally expressed in adipose ...

OBJECTIVE: Synthetic ligands for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) improve insulin sensitivity in obesity, but it is still unclear whether inflammatory signals modulate their metabolic actions. In this study, we tested whether targeted disruption of inducible nitric oxide (NO) synthase (iNOS), a key inflammatory mediator in obesity, modulates the metabolic effects ...

Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central to the development of effective means to combat obesity. Here we identify CaMKK2 as a component of one of these pathways, show that ...

It is generally considered that 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have renoprotective effects via a pathway independent of their cholesterol-lowering cascade. In the kidneys of diabetic nephropathy, monomeric endothelial nitric oxide synthase (eNOS) is thought to be overexpressed; and its dimerization is suppressed. In the present study, we investigated the ...

The goal of this study was to determine whether inhibiting the renin-angiotensin system would restore insulin signaling and normalize substrate use in hearts from obese ob/ob mice. Mice were treated for 4 wk with Captopril (4 mg/kg x d). Circulating levels of free fatty acids, triglycerides, and insulin were measured ...

Adiponectin has been proposed to act as an antidiabetic adipokine, suppressing gluconeogenesis and stimulating fatty acid oxidation in the liver and skeletal muscle. Although adiponectin-knockout (adipo(-/-)) mice are known to exhibit insulin resistance, the degrees of insulin resistance and glucose intolerance are unexpectedly only moderate. In this study, the adipo(-/-) ...

We examined male and female glucose transporter isoform-3 (GLUT3; placenta)-null heterozygous(+/-) mutation-carrying mice and compared them with age- and sex-matched wild-type(+/+) littermates. No difference in postnatal (1-2 days, 6-7 days, 12-13 days, 20-21 days), postsuckling (1-2 mo), and adult (3-6 mo) growth pattern was seen except for an increase in ...

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide implicated in several metabolic functions, including insulin secretion and sympathoadrenal activation. To clarify the roles of PACAP in maintenance of whole-body glucose and lipid homeostasis, the impact of the deletion of PACAP on glucose homeostasis, body weight, and adipose tissue mass was ...

We examined the endothelial gap junctions in diabetic hyperlipidemic mice. Male apolipoprotein E (apoE)-deficient mice were made diabetic by streptozotocin. Three weeks later, the animals were treated with simvastatin for 2 weeks. The expression of aortic gap junctions in the non-diabetic (n=10), untreated diabetic (n=10), and simvastatin-treated diabetic animals (n=6) ...

AIM: To investigate the effects of ghrelin on delayed gastrointestinal transit in alloxan-induced diabetic mice. METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice group and diabetic mice group treated with ghrelin at doses of 0, 20, 50, ...

We hypothesized that the apolipoprotein mimetic peptide L-4F, which induces arterial anti-oxidative enzymes and is vasoprotective in a rat model of diabetes, would ameliorate insulin resistance and diabetes in obese mice. L-4F (2 mg/kg/d) administered to ob/ob mice for 6 weeks limited weight gain without altering food intake, decreased visceral ...

BACKGROUND: Disorder of the extracellular matrix has been suggested to play a role in the development of diabetic nephropathy. The aim of the present study was to examine the expression of matrix metalloproteinase-9 (MMP-9) in the kidney of Kkay mice, a type 2 diabetic model. METHODS: Eight Kkay control mice ...

Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 ...

Endothelin-1 (1-31) [ET-1 (1-31)], a novel member of the ET family, comprises 31 amino acids and is derived from the selective hydrolysis of big ET-1 by chymase. Although ET-1 (1-31) reportedly exerts biological effects by direct or indirect [via its conversion to ET-1 (1-21)] mechanisms, it is unclear whether in ...

Obesity and diabetes, termed "diabesity," are serious health problems that are increasing in frequency. However, the molecular mechanisms and neuronal regulation of these metabolic disorders are not fully understood. We show here that Shp2, a widely expressed Src homology 2-containing Tyr phosphatase, plays a critical role in the adult brain ...

OBJECTIVE: To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains. RESEARCH DESIGN AND METHODS: Hyperinsulinemic-euglycemic (approximately 8.5 mmol/l) and -hypoglycemic (approximately 3.0 mmol/l) clamps were done in catheterized, 5-h-fasted mice to assess insulin action and hypoglycemic counter-regulatory responsiveness. Hyperglycemic clamps (approximately 15 mmol/l) were done to ...

OBJECTIVE: Chromium has gained popularity as a nutritional supplement for diabetic patients. This study evaluated the effect of chronic administration of a chromium complex of D-phenylalanine (Cr(D-phe)(3)) on glucose and insulin tolerance in obese mice. The study tested the hypothesis that Cr(D-phe)(3) suppresses endoplasmic reticulum (ER) stress and insulin resistance ...

We investigated the effects of chronic simvastatin treatment on the impaired endothelium-dependent relaxation seen in aortas from type 2 diabetic mice. Starting at 8 weeks of diabetes, simvastatin (10 mg/kg per day) was administered to diabetic mice for 4 weeks. The significantly elevated systolic blood pressure in diabetic mice was ...

We have examined the metabolic effects of daily administration of carbenoxolone (CBX), a naturally occurring 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) inhibitor, in mice with high fat diet-induced insulin resistance and obesity. Eight-week-old male Swiss TO mice placed on a synthetic high fat diet received daily intraperitoneal injections of either saline vehicle or ...

Corosolic acid (CRA), a constituent of Banaba leaves, has been reported to exert anti-hypertension, anti-hyperinsulinemia, anti-hyperglycemia, and anti-hyperlipidemia effects as well as to induce anti-inflammatory and anti-oxidative activities. The aim of this study was to investigate the inhibitory effects of CRA on the development of obesity and hepatic steatosis in ...

BACKGROUND: The combined treatment of sustained-release basic fibroblast growth factor (Sr-bFGF) and a 5-hydroxytryptamine(2A) blocker, sarpogrelate, was evaluated to see whether it reversed the impaired collateral circulation in diabetic (DM) mouse hindlimb ischemia. METHOD AND RESULTS: Diabetic and normal mice with ischemic hindlimb were randomly assigned to 1 of 5 ...

A novel preparation of a dialysed aqueous extract of fenugreek seeds (FSE) that stimulates the insulin signalling pathway was reported previously (Vijayakumar et al., 2005). The present study was designed to investigate the long-term effects (multiple dose effect) of this FSE preparation on the blood glucose level and body weight, ...

Maxadilan and its truncated variant, M65, are agonist and antagonist specific, respectively, for the PAC1 receptor. PAC1 is the specific receptor for the pituitary adenylate cyclase-activating peptide (PACAP), which is not shared by vasoactive intestinal peptide (VIP). PACAP is a ubiquitous peptide of the glucagon superfamily that is involved in ...

OBJECTIVE: We hypothesized that the induction of heme oxygenase (HO)-1 and increased HO activity, which induces arterial antioxidative enzymes and vasoprotection in a mouse and a rat model of diabetes, would ameliorate insulin resistance, obesity, and diabetes in the ob mouse model of type 2 diabetes. RESEARCH DESIGN AND METHODS: ...

Metabolomics is a powerful tool for identifying both known and new disease-related perturbations in metabolic pathways. In preclinical drug testing, it has a high potential for early identification of drug off-target effects. Recent advances in high-precision high-throughput mass spectrometry have brought the metabolomic field to a point where quantitative, targeted, ...

The Vanadium uptake by Coprinus comatus and their co-effect on hyperglycemic mice were studied. By fermentation and AAS analysis, the optimal concentration of vanadium in medium was 0.4%, and the content of vanadium accumulated in the mycelia was 3,528.0 microg/g. At the concentration of 0.4%, the vanadium-associated toxicity was reduced, ...

Recent data suggest that the gut microbiota plays a significant role in fat accumulation. However, it is not clear whether gut microbiota is involved in the pathophysiology of type 2 diabetes. To assess this issue, we modulated gut microbiota via antibiotics administration in two different mouse models with insulin resistance. ...

INTRODUCTION: With the large-scale availability of transgenic and knockout mouse models, the use of mice may greatly facilitate the examination of the mechanisms underlying diabetic erectile dysfunction (ED). Although in vitro studies of the mouse cavernosum show impairment of vasoreactivity, to date, no studies have demonstrated the in vivo impairment ...

AIM OF THE STUDY: The antihyperglycemic and antilipidperoxidative effects of the dry matter of culture broth (DMCB) of Inonotus obliquus were investigated. MATERIALS AND METHODS: The normal, glucose-induced hyperglycemic and alloxan-induced diabetic mice were used to evaluate the antihyperglycemic and antilipidperoxidative effects of the DMCB of Inonotus obliquus. RESULTS: Treatment ...

To determine the relative contribution of obesity and visceral white adipose tissue (WAT) to metabolic syndrome, we developed a model that is susceptible to high-fat diet-induced obesity and insulin resistance using male KK/Ta mice. The ratio of WAT weight to body weight was greater in the high-fat diet group compared ...

Mitochondrial fatty acid oxidation (mFAO) is considered to be essential for driving gluconeogenesis (GNG) during fasting. However, quantitative in vivo data on de novo synthesis of glucose-6-phosphate upon acute inhibition of mFAO are lacking. We assessed hepatic glucose metabolism in vivo after acute inhibition of mFAO by 30 mg kg(-1) ...

The stimulatory G protein Gsalpha transmits signals from activated beta-adrenergic receptors via the cyclic AMP-PKA pathway, targeting the key regulatory protein phospholamban. We hypothesized that mice with intrinsic activation of cardiac Gsalpha are resistant to the development of the diabetic cardiomyopathy phenotype. Accordingly, streptozotocin (STZ)-diabetes mellitus was induced in genetically ...

This study was conducted to investigate whether retinoic acids (RAs) had any effect on apoptosis during the development of diabetic retinopathy. To investigate whether RAs had any effect on apoptosis during the development of diabetic retinopathy, we housed 32 C57BL/6 male mice and induced diabetes in 24 by intra peritoneal ...

Maternal diabetes leads to an adverse in utero environment, but whether maternal diabetes impairs nephrogenesis is unknown. Diabetes was induced with streptozotocin in pregnant Hoxb7-green fluorescence protein mice at embryonic day 13, and the offspring were examined at several time points after birth. Compared with offspring of nondiabetic controls, offspring ...

OBJECTIVE: Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, ...

Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in beta-cells. Although UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to beta-cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum ...

Serum retinol-binding protein (RBP4) is secreted by liver and adipocytes and is implicated in systemic insulin resistance in rodents and humans. RBP4 normally binds to the larger transthyretin (TTR) homotetramer, forming a protein complex that reduces renal clearance of RBP4. To determine whether alterations in RBP4-TTR binding contribute to elevated ...

Obese leptin-deficient (ob/ob) mice have increased levels of high-density lipoprotein (HDL) and a unique lipoprotein referred to as low-density lipoprotein (LDL)/HDL1. When crossed onto an apolipoprotein AI (apoAI)-deficient (-/-) background, ob/ob;apoAI-/- mice accumulate LDL/HDL1 in the absence of traditional HDL. To determine the role of LDL/HDL1 in atherosclerosis, C57BL/6, apoAI-/-, ...

Mammalian 14-3-3 proteins are dimeric phosphoserine-binding proteins that participate in signal transduction and regulate several aspects of cellular biochemistry. Diabetic cardiomyopathy is associated with increased oxidative stress and inflammation. In order to study the pathogenic changes underlying diabetic cardiomyopathy, we examined the role of 14-3-3 protein and apoptosis signal-regulating kinase ...

Glucose homeostasis is achieved by triggering regulation of glycogen synthesis genes in response to insulin when mammals feed, but the underlying molecular mechanism remains largely unknown. The aim of our study was to examine the role of the signal transducers and activators of transcription 3 (STAT3) in insulin signaling. We ...

AIMS/HYPOTHESIS: Orexin/hypocretin is a hypothalamic neuropeptide that regulates motivated behaviours, such as feeding and arousal, and, importantly, is also involved in energy homeostasis. The aim of this study was to reveal the role of orexin in the regulation of insulin sensitivity for glucose metabolism. METHODS: Orexin knockout mice fasted overnight ...