apelin-13-peptide and Diabetes-Mellitus--Type-2

There is no clear information about the level of Apelin-13 in patients with diabetic nephropathy (DN). In this study, we investigated whether there is a relationship between Apelin-13 level and the severity of the disease in patients with DN.. In our case-control study, we included patients who applied to the endocrinology outpatient clinic in 2019. Patients without a history of diabetes were determined as the healthy group (group 1). The patients were divided into 4 groups according to their microalbumin and creatinine levels. Venous blood samples were obtained from all patients for routine laboratory parameters and Apelin-13 levels. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) for insulin resistance was calculated using the formula: plasma glucose X insulin level/405.. Albumin was found to be significantly lower in group 5 (p = 0.032), hemoglobin A1c, microalbumin/creatinine and HOMA-IR values were found to be significantly lower in group 1 (p < 0.001 for each). Apelin-13 level was found to be significantly higher in group 4 and group 5 (p < 0.001). A negative correlation was found between Apelin-13 and GFR (r = - 0.286, p = 0.003). A positive correlation was found between Apelin-13 and HOMA-IR (r = 0.309, p = 0.009) and microalbumin/creatinine (r = 0.296, p < 0.001).. In patients with DN, Apelin-13 level increases with the severity of the disease and can be used as a biomarker for staging of DN.

Topics: Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Insulin Resistance

Apelin, a new identified adipokine, and its G protein-coupled receptor named APJ are widely expressed in various tissues. Apelin has been found to play important roles in the physiopathology of multiple diseases. Our aim is to assess the effect of long-term apelin treatment on serum insulin level and pancreatic islet beta-cell mass in the late stage of type 2 diabetes without hyperinsulinemia and to investigate the role of apelin in myocardial fatty acid and glucose metabolism. In the present study, the high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats were given once daily intraperitoneal injection of apelin-13 (0.1 μmol/kg) for 10 weeks. We observed that apelin significantly improved serum insulin reduction and reduced hyperglycemia. Histologic analysis showed that long-term apelin treatment significantly increased pancreatic islet beta cell mass. Exogenous apelin failed to change dyslipidaemia of type 2 diabetic rats. Apelin treatment markedly decreased elevated myocardial FFA and glycogen content. Treatment of type 2 diabetic rats with apelin markedly reduced increased gene expressions of the cardiac fatty acid transporter CD36, CPT-1, and Peroxisome proliferator-activated receptor (PPAR)-α. Whereas the gene levels of citrate synthase and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α), a transcriptional coactivator, mediating mitochondrial biogenesis in heart were unaltered in response to exogenous apelin. Taken together, longer-term apelin treatment prevented pancreatic beta-cell loss or failure in experimental type 2 diabetic rats. Apelin can regulate myocardial metabolism. Apelin reduced myocadial fatty acid uptake and oxidation through inhibiting PPAR-α but did not affect myocardial mitochondrial biogenesis in type 2 diabetic rats.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Dyslipidemias; Fatty Acids; Glucose; Insulin; Insulin-Secreting Cells; Intercellular Signaling Peptides and Proteins; Male; Myocardium; Rats, Wistar

To investigate the chronic effects of twice-daily administration of stable apelin analogues, apelin-13 amide and pyroglutamyl (pGlu) apelin-13 amide, on metabolic variables in glucose-intolerant and insulin-resistant diet-induced obese mice fed a high-fat diet for 150 days.. Groups of mice received twice-daily (9 am and 5 pm) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1-39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity, together with pancreatic hormone content and biochemical variables such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry analysis and indirect calorimetry were also performed.. Administration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased body weight, food intake and blood glucose and increased plasma insulin compared with high-fat-fed saline-treated controls (P < .05 and P < .001), Additionally, all peptide-treated groups exhibited improved glucose tolerance (oral and intraperitoneal), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved glycated haemoglobin and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio, whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased glucagon-like peptide-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL cholesterol and total body fat, and increased pancreatic insulin content.. These data indicate the therapeutic potential of stable apelin-13 analogues, with effects equivalent to or better than those of exendin-4.

Topics: Adiposity; Amides; Animals; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Diet, High-Fat; Drug Stability; Energy Intake; Energy Metabolism; Exenatide; Glucagon-Like Peptide-1 Receptor; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Male; Mice; Obesity; Weight Loss

Apelin has been reported to be associated with multiple physiological processes in the cardiovascular system. The aim of the present study was to investigate the effects of Apelin‑13 administration on cardiac function, hyperglycemia, insulin resistance (IR), dyslipidemia, endothelial function, inflammation and glucose metabolism in type 2 diabetic Goto‑Kakizaki (GK) rats, and compare the protective effects of Apelin‑13 with metformin or atorvastatin. In the present study, type 2 diabetes was induced in male Goto‑Kakizaki (GK) rats fed with high‑fat diet (HFD). Simultaneously, the rats were treated with metformin (350 mg/kg/d, by gavage), atorvastatin (50 mg/kg/d, by gavage) or Apelin‑13 (200 µg/kg/d, intraperitoneal injection) once daily for 4 consecutive weeks. Hemodynamic parameters were examined by RM6240BD multi‑channel physiological signal monitoring. Fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment for insulin resistance (HOMA‑IR), total cholesterol (TC), triglyceride (TG), high density lipoprotein‑cholesterol (HDL‑C), low density lipoprotein‑cholesterol (LDL‑C), endothelin‑1 (ET‑1), nitric oxide (NO), constitutive nitric oxide synthase (cNOS) activity, tumor necrosis factor‑α (TNF‑α), leptin and Apelin‑12 levels were measured. Western blotting was performed to determine the levels of Apelin‑12, glucose transporter 4 (GLUT4) and phosphorylated (p)‑5'adenosine monophosphate‑activated protein kinase (AMPK) α2. It was demonstrated that Apelin‑13 decreased heart rate, left ventricular end‑diastolic pressure, FPG, FINS, HOMA‑IR, TC, TG, LDL‑C, ET‑1, TNF‑α and leptin, whereas it increased the rise and fall of maximum rate of left ventricular pressure, HDL‑C, NO, cNOS activity and Apelin‑12 compared with the GK‑HFD group. In addition, GLUT4 and p‑AMPKα2 levels in myocardial tissues were elevated by administration of Apelin‑13. This protective effect of Apelin‑13 was comparable to that of metformin or atorvastatin. Overall, the present study demonstrated that administration ofApelin‑13 may be a promising therapeutic agent for the treatment of type 2 diabetes and metabolic syndrome.

Topics: Animals; Atorvastatin; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Heart Function Tests; Hemodynamics; Intercellular Signaling Peptides and Proteins; Lipid Metabolism; Male; Metformin; Oxidation-Reduction; Protective Agents; Rats