glucagon-like-peptide-1 and Proteinuria

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Glucagon-like peptide-1 (GLP-1) is one of the incretins, gut hormones released from the intestine in response to food intake. GLP-1 receptor (GLP-1R) agonists have been used to treat type 2 diabetes. Here, we studied the effect of the administration of a GLP-1R agonist, liraglutide, on proteinuria and the progression of overt DN in type 2 diabetic patients. Twenty-three type 2 diabetic patients with overt DN, who had already been treated with blockade of renin-angiotensin system under dietary sodium restriction, were given liraglutide for a period of 12 months. Treatment with liraglutide caused a significant decrease in HbA1c from 7.4 ± 0.2% to 6.9 ± 0.3% (p = 0.04), and in body mass index (BMI) from 27.6 ± 0.9 kg/m² to 26.5 ± 0.8 kg/m² after 12 months (p < 0.001), while systolic blood pressure did not change. The progression of DN was determined as the rate of decline in estimated glomerular filtration rate (eGFR). The 12-month administration of liraglutide caused a significant decrease in proteinuria from 2.53 ± 0.48 g/g creatinine to 1.47 ± 0.28 g/g creatinine (p = 0.002). The administration of liraglutide also substantially diminished the rate of decline in eGFR from 6.6 ± 1.5 mL/min/1.73 m²/year to 0.3 ± 1.9 mL/min/1.73 m²/year (p = 0.003). Liraglutide can be used not only for reducing HbA1c and BMI, but also for attenuating the progression of nephropathy in type 2 diabetic patients.

Topics: Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Female; Glomerular Filtration Rate; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Liraglutide; Male; Middle Aged; Proteinuria; Receptors, Glucagon; Systole

The aim of the present study is to investigate the antidiabetic properties of oligosaccharides of Ophiopogonis japonicus (OOJ) in experimental type 2 diabetic rats. OOJ was administered orally in doses of 225 and 450 mg/kg body weight to high-fat diet and low-dose streptozotocin (STZ)-induced type 2 diabetic rats for 3 weeks. The results showed that OOJ treatment could increase body weight, decrease organ related weights of liver and kidney, reduce fasting blood glucose level, and improve oral glucose tolerance in diabetic rats. Moreover, increased glycogen content in liver and skeletal muscle, reduced urinary protein excretion, higher hepatic GCK enzyme activity, lower hepatic PEPCK enzyme activity, enhanced GLP-1 level, decreased glucagon level and alleviated histopathological changes of pancreas occurred in OOJ-treated diabetic rats by comparison with untreated diabetic rats. This study demonstrates, for the first time to our knowledge, that OOJ exerts remarkable antidiabetic effect in experimental type 2 diabetes mellitus, thus justifying its traditional usage.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Fasting; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glycogen; Hypoglycemic Agents; Liver; Male; Muscle, Skeletal; Oligosaccharides; Ophiopogon; Organ Size; Proteinuria; Rats; Rats, Sprague-Dawley

It is well known that rats and mice, when fed a high-fat diet, develop obesity associated with abnormal glycolipid metabolism. In this study, we investigated the effects of a high-fat diet on a diabetic rat model, Spontaneously Diabetic Torii (SDT), which develops diabetes due to decreased insulin production and secretion with age. We hypothesized that a high-fat diet would accelerate the induction of diabetes in this model. The SDT rats were divided into 2 groups, which were fed a high-fat diet or standard diet for 16 weeks. The group fed a high-fat diet developed obesity, hyperinsulinemia, and hyperlipidemia until 16 weeks of age. Before 16 weeks of age, hyperglycemia accompanied by hypoinsulinemia developed in the group on a standard diet, but serum glucose levels were comparable in both groups. After 16 weeks of age, the group on a standard diet showed an increase in serum glucose levels and a decrease in serum insulin levels. Unexpectedly, in the group on the high-fat diet, we observed a suppressed of the progression of hyperglycemia/hypoinsulinemia. Histopathological observation revealed more pancreatic beta cells in the group on the high-fat diet. This study suggests that feeding SDT rats a high-fat diet induces obesity, hyperinsulinemia, and hyperlipidemia, but not hyperglycemia, until 16 weeks of age. Thereafter, age-dependent progress of hyperglycemia and hypoinsulinemia was delayed by a high-fat diet. The hyperfunction of pancreatic beta cells induced by a high-fat diet before the onset of hyperglycemia appears to suppress development of hyperglycemia/hypoinsulinemia.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diet; Dietary Fats; Energy Intake; Glucagon-Like Peptide 1; Glucose Tolerance Test; Insulin; Male; Pancreas; Proteinuria; Rats