Aims - Sodium glucose cotransporter-2 (SGLT-2) is key to reabsorption of glucose in the kidney. SGLT-2 inhibitors are in clinical development for treatment of type 2 diabetes mellitus (T2DM). The mechanism may be of value also in the treatment of type 1 diabetes mellitus (T1DM). This study investigated effects of ...

Background Recent evidence from case reports, observational studies, and randomized trials suggests that long-term use of antidepressants increases the risk of developing diabetes. However, the nature of the relationship between antidepressants and diabetes remains unclear. Objective To determine whether there is an association between antidepressant use and the risk of ...

Diabetic neuropathy is recognized as one of the most common complications of chronic diabetes, but its pathophysiological mechanism is complex and yet to be completely explored. Monotherapy with conventional analgesics fails to provide adequate pain relief in peripheral diabetic neuropathy. There are a number of evidence suggesting that tumor necrosis ...

Objective: Diabetic patients are at risk of macro- and micro-vascular complications, including diabetic nephropathy, and have difficulties in achieving blood pressure (BP) goals. Aliskiren, a direct renin inhibitor, inhibits the first step of the renin angiotensin aldosterone system. We aimed to systematically address the relevant evidence on the effects of ...

Glucagon-like peptide-1 (GLP-1), a gut derived hormone secreted in response to nutrients, has several glucose and weight regulating actions including enhancement of glucose stimulated insulin secretion, suppression of glucagon secretion, slowing of gastric emptying, and reduction in food intake. Due to these multiple effects, the GLP-1 receptor system has become ...

Dyslipidemia is common in patients with type 2 diabetes. Statins are used as the first choice in treatment of diabetic dyslipidemia. Atorvastatin represents a first-line treatment option, alongside other hydroxyl methylglutaryl coenzyme A reductase inhibitors. Repaglinide is a short-acting, oral, insulin secretagogue that is used in the treatment of type ...

Excessive activity of hepatic atypical protein kinase (aPKC) is proposed to play a critical role in mediating lipid and carbohydrate abnormalities in obesity, the metabolic syndrome, and type 2 diabetes mellitus. In previous studies of rodent models of obesity and type 2 diabetes mellitus, adenoviral-mediated expression of kinase-inactive aPKC rapidly ...

Dipeptidyl peptidase-4 (DPP-4) inhibitors are some of the newest medications in our armamentarium for the management of type 2 diabetes mellitus. Through inhibition of the DPP-4 enzyme, these agents increase the amount of circulating incretin hormones, leading to an increase in insulin release and a suppression of glucagon secretion. Linagliptin ...

Introduction: Dipeptidylpeptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). Areas covered: This paper is an updated review, providing an analysis of both the similarities and the differences between the various compounds known as gliptins, currently used in the clinic (sitagliptin, vildagliptin, saxagliptin, alogliptin and ...

Introduction: Increasing population age, obesity and physical inactivity mean that type 2 diabetes mellitus (T2DM) is increasingly common. Current treatments may be limited by adverse events, drug-drug interactions or contraindication/need for dose adjustment in patients with renal impairment. Areas covered: This paper reviews studies that evaluate the pharmacokinetics, pharmacodynamics and ...

Introduction: Metformin is considered as the first-line drug therapy for the management of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors, by promoting insulin secretion and reducing glucagon secretion in a glucose-dependent manner, offer new opportunities for oral therapy after failure of metformin. Areas covered: An updated review of the literature ...

ABSTRACT: BACKGROUND: Glucose fluctuations including robust postprandial hyperglycemia are a risk for promoting atherosclerosis and diabetic complications. The alpha-glucosidase inhibitors and the dipeptidyl peptidase-4 (DPP-4) inhibitors have been found to effectively decrease postprandial hyperglycemia independently. Therefore, glycemic control with the combination of these drugs is warranted. METHODS: Continuous glucose monitoring ...

Renin-angiotensin-aldosterone system inhibitors prevent the progression of kidney disease in patients with diabetic nephropathy, and we studied how that benefit varies by the type of diabetes and baseline urinary albumin. We pooled data from 49 randomized controlled trials in a meta-analysis using the ratio of endpoint urinary albumin levels in ...

Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a ...

To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. A cross-sectional study of consecutive in-patients admitted to hospital in any department during the first semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a ...

Treating high fat fed/low dose streptozotocin-diabetic rats; model of type 2 diabetes, with ilepatril (vasopeptidase inhibitor, blocks neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE)) improved vascular and neural functions. Next, studies were performed to determine the individual effect of inhibition of NEP and ACE on diabetes-induced vascular and neural ...

Although being a primary objective in the management of type 2 diabetes, optimal glycaemic control is difficult to achieve and usually not maintained over time. Type 2 diabetes is a complex pathology, comprising altered insulin sensitivity and impaired insulin secretion. Recent advances in the understanding of the physiological functions of ...

Aims: Acute hyperglycaemia induces coagulation activation in diabetes patients. We hypothesized that rapid-acting insulin has a beneficial postprandial effect on coagulation and fibrinolysis compared with intermediate-acting insulin due to its ability to lower postprandial hyperglycaemia. Materials and Methods: This was tested in a parallel controlled study in well-controlled patients with ...

An increased prevalence of diabetes mellitus (DM) has been reported in patients with primary aldosteronism (PA). DM is associated with abnormal structure and metabolism of circulating lipoproteins, which normally serve as a major source of cholesterol for adrenocortical steroidogenesis. The present study has been designed to investigate the effect of ...

The aim of the present study was to evaluate the relationships between the islet blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For measuring pancreatic and islet blood a non-radioactive microsphere technique was used. Vehicle pre-treatment of glucose administered diabetic ...

ABSTRACT: BACKGROUND: Tartary buckwheat bran is an important natural source of quercetin and isoquercetin. Quercetin and isoquercetin are both powerful alpha-glucosidase inhibitors. Although the IC50 of isoquercetin as alpha-glucosidase inhibitor was much higher than that of quercetin, the bioavailability of isoquercetin was higher than that of quercetin. Hence, we are ...

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycemic control without causing weight gain or increasing hypoglycemic risk in patients with type 2 diabetes (T2DM). The efficacy and tolerability of saxagliptin, a once-daily DPP-4 inhibitor, administered as monotherapy, as add-on therapy to metformin, a sulfonylurea, ...

PURPOSE: To determine whether there is an association between antidepressant use and the risk of developing type 2 diabetes. METHODS: This study was a retrospective cohort analysis using the Texas Medicaid prescription claims database. Data were extracted for new users of either antidepressant agents (exposed) or benzodiazepines (unexposed) from January ...

Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the ...

Patients with diabetes mellitus (DM) have a high prevalence of coronary artery disease (CAD), as diabetes is implicated in the formation of atherosclerotic plaque. Endothelial dysfunction is one of the precursor key steps in the development of atherosclerosis in diabetic subjects. Decreased nitric oxide (NO) production, increased oxidative stress and ...

Objectives  Phosphodiesterase type 5 inhibitors are potent in relieving erectile dysfunction (ED), however, they are less satisfactory in diabetic patients, probably due to the pro-inflammatory biomarkers caused by diabetes. Therefore, it was interesting to compare the effects of sildenafil with strontium fructose 1,6-diphosphate (FDP-Sr) on cavernosal vascular activity and expressions ...

BACKGROUND.: Pancreatic acinar cells are commonly cotransplanted along with islets during auto- and allotransplantations. The aims of this study were to identify how acinar cell proteases cause human islet cell loss before and after transplantation of impure islet preparations and to prevent islet loss and improve function with supplementation of ...

BACKGROUND: Glucose absorption postprandially increases markedly to levels far greater than possible by the classic glucose transporter sodium-glucose cotransporter 1 (SGLT1). HYPOTHESIS: Luminal concentrations of glucose >50 mM lead to rapid, phenotypic, non-genomic adaptations by the enterocyte to recruit another transporter, glucose transporter 2 (GLUT2), to the apical membrane to increase ...

OBJECTIVE: The effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial. We thus determined the concentration of atherogenic small, dense LDL (sdLDL) in patients with type 2 diabetes and an elevated cardiovascular risk profile. RESEARCH DESIGN AND METHODS: Multicenter, randomized, ...

To test the effect of insulin on renal perfusion and the participation of nitric oxide and prostaglandins as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flowprobes around renal arteries and with a systemic arterial pressure (SAP, n = 4) ...

Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Various pathways in addition to the renin-angiotensinogen system have been implicated in the pathogenesis of diabetic nephropathy. Strategies to interrupt these pathophysiological pathways are a key to the development of new targeted therapies to prevent progression of diabetic ...

A patient with a 17-year history of plaque psoriasis accompanied by type 2 diabetes mellitus discontinued cyclosporine and steroid ointment given for treatment of psoriasis because she was dissatisfied with the effects of the drugs. After sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, was administered for control of blood glucose, psoriatic ...

The incretin system plays an important role in glucose homeostasis, largely through the actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Unlike GIP, the actions of GLP-1 are preserved in patients with type 2 diabetes mellitus, which has led to the development of injectable GLP-1 receptor (GLP-1R) agonists ...

Dapagliflozin is a highly selective sodium-glucose co-transporter 2 inhibitor developed for the treatment of Type 2 diabetes mellitus. Its inhibition of sodium-glucose co-transporter 2 blocks glucose reabsorption in the proximal tubule of the kidney, increasing renal glucose excretion via the urine, resulting in reduction of glycated hemoglobin, fasting plasma glucose ...

Dipeptidyl peptidase (DPP) IV inhibitors are likely beneficial for treating diabetic complication and modulating glucagon-like peptide-1 receptor (GLP-1R) expression. The aim of this study was to determine if the DPP IV inhibitor, LAF237, has renoprotective qualities in streptozotocin-induced diabetic rats. Diabetic and non-diabetic rats were treated with an oral dose ...

Asia bears the world's greatest burden of type 2 diabetes (T2DM) and prevalence is increasing rapidly. Compared to other races, Asians develop T2DM younger, at a lower degree of obesity, suffer longer from its complications and die earlier. Curbing this epidemic requires an integrated, risk-based, and multidisciplinary approach. Inadequately managed ...

Type 1 diabetes is considered to be an autoimmune disease in which T cells attack pancreatic islet cells. Impaired glucose tolerance with type 2 diabetes has been classified as an obesity-associated metabolic syndrome. However, recent studies have revealed that type 2 diabetes is an autoinflammatory disease due to an imbalance ...

AIM: To characterize the pharmacodynamic profile of DA-1229, a novel dipeptidyl peptidase (DPP) 4 inhibitor. MAIN METHODS: Enzyme inhibition assays against DPP4, DPP8 and DPP9. Antidiabetic effects of DA-1229 in HF-DIO mice and young db/db mice. KEY FINDINGS: DA-1229 was shown to potently inhibit the DPP4 enzyme in human and ...

Context:Traditional lipid measures are known to be associated with incident type 2 diabetes.Objective:Our objective was to assess the independent association between lipid profiles and the development of type 2 diabetes in nondiabetic Korean subjects over a 4-yr period.Design and Methods:A total of 5577 Koreans without diabetes who underwent consecutive comprehensive ...

Obesity and diabetes once considered 'rich man's diseases' are one of the biggest public health challenges of the 21st century. Obesity being a gateway to diabetes is a global problem. The supporting statistics are alarming since diabetes is reaching pandemic proportion all over the world. Eighty percent of all patients ...

Aims: Empagliflozin is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study assessed acute pharmacological properties of empagliflozin in vitro and pharmacokinetic properties in vivo and compared its potency and selectivity with other SGLT-2 inhibitors. Materials and Methods: [(14) ...

Roganović J, Radenković M, Tanić N, Tanić N, Petrović N, Stojić D. Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit. Eur J Oral Sci 2011; 119: 352-360. © 2011 Eur J Oral Sci The aim of this study was to assess the effect of ...

Diabet. Med. 28, 1176-1181 (2011) ABSTRACT: Aims  Patients with Type 1 diabetes have significantly elevated postprandial glucagon secretion. Dipeptidyl peptidase IV inhibitors improve HbA(1c) by several mechanisms, including increasing glucagon-like peptide 1 and glucose-dependent insulinotropic peptide concentrations, which decreases postprandial rises in glucagon in both Type 1 and Type 2 diabetes. This study evaluates the ...

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin deficiency or resistance. Management starts with single oral antidiabetic drug (OAD) but eventually switch over to combination therapy because of progressive β-cell dysfunction. Hypoglycemia, weight gain, and adverse cardiovascular events are major limitations of the available OADs (Sulfonylureas ...

Hypertension occurs twice as commonly in diabetics than in comparable nondiabetics. Patients with both disorders have a markedly higher risk for premature microvascular and macrovascular complications. Aggressive control of blood pressure (BP) reduces both micro- and macrovascular complications. In diabetic hypertensives, angiotensin converting enzyme inhibitors (ACEIs) are the first line ...

AIMS: Associations of proinsulin-to-insulin ratios with incident type 2 diabetes have been inconsistent. The use of C-peptide as the denominator in the ratio may allow for better prediction because C-peptide concentration is not affected by hepatic insulin clearance. The objective of this paper was to compare fasting intact and split ...

Aim: We assessed the efficacy of 8 classes of diabetes medications used in current clinical practice (metformin, sulfonylureas, α-glucosidase inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 analogs, and insulin analogs) to reach the HbA1c target <7% in type 2 diabetes. Methods: MEDLINE, EMBASE, and the Cochrane CENTRAL were searched ...

The maintenance of normal glucose homeostasis requires a complex, highly integrated interaction among the liver, muscle, adipocytes, pancreas and neuroendocrine system. Recent studies have demonstrated that the kidneys also play a central role in glucose homeostasis by reabsorbing all of the filtered glucose, an adaptive mechanism that ensures sufficient energy ...

Maternal diabetes increases the risks for embryo malformations. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are two relevant MMPs for embryo development. Here, we addressed whether changes in these MMPs and in tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 are altered in embryos and decidua from type 1 diabetic rats during ...

Protease inhibitors (PIs), such as atazanavir sulfate and ritonavir, are used clinically to prevent the progression of HIV and are known to induce insulin resistance. To determine whether PI-mediated insulin resistance is induced by activation of pro-inflammatory cascades, L6 skeletal muscle cells were treated ±atazanavir sulfate, ritonavir, or atazanavir sulfate+ritonavir, ...