Berberis aristata, Elaeis guineensis and Coffea canephora Extracts Modulate the Insulin Receptor Expression and Improve Hepatic Steatosis in NAFLD Patients: A Pilot Clinical Trial.

Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and diabetes. A reduction in insulin receptor (IR) expression has been reported in these patients. The aims of this study were to evaluate the effects of a mixture of plant extracts consisting of Berberis aristata, Elaeis guineensis and decaffeinated green coffee by Coffea canephora on the improvement of glycaemic profile, through the modulation of IR levels, and of hepatic steatosis in NAFLD patients. Forty-nine patients with a grade of steatosis S1-S2 were randomly allocated to the treatment with plant extracts or placebo for six months. Hepatic steatosis was evaluated using transient elastography with CAP (controlled attenuation parameter). Glucose, insulin, and IR levels were measured in serum samples. At the end of the study, patients treated with plant extracts displayed a significant reduction of serum glucose (p < 0.001), insulin levels (p < 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), and CAP value (p < 0.01) compared to placebo. Moreover, the IR expression was increased significantly in the plant extracts group compared to the placebo group (p < 0.05). The combination of plant extracts increases serum IR levels, determining amelioration of glycemic profile and improvement of hepatic steatosis in NAFLD patients.

Yangxin Tongmai Formula ameliorates impaired glucose tolerance in children with Graves' disease through upregulation of the insulin receptor levels.

Graves' disease (GD) is the leading cause of hyperthyroidism, and the majority of GD patients eventually develop disorders of glucose handling, which further affects their quality of life. Yangxin Tongmai formula (YTF) is modified from a famous formula of traditional Chinese medicine for the treatment of cardiovascular diseases. In this study we investigated the potential effects of YTF in the treatment of pediatric GD patients with impaired glucose tolerance. Forty pediatric GD patients and 20 healthy children were recruited for this clinical study. Based on the glucose tolerance, the GD patients were divided into two groups: 20 patients displayed impaired glucose tolerance, while the other 20 patients displayed normal glucose tolerance. YTF was orally administered for 60 days. YTF administration significantly ameliorated the abnormal glucose tolerance and insulin sensitivity in the GD patients with impaired glucose tolerance. To determine the molecular mechanisms of this observation, the number of plasma insulin receptors was determined by ELISA. Before treatment, the fasting and postprandial levels of the insulin receptor were significantly lower in patients with impaired glucose tolerance compared with those in patients with normal glucose tolerance and healthy children. After YTF treatment, both the fasting and the postprandial circulating insulin receptor levels were upregulated, and close to those in healthy children. Therefore, YTF is a potential effective treatment to enhance glucose handling in GD children with impaired glucose tolerance.

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism.

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

Oat consumption reduced intestinal fat deposition and improved health span in Caenorhabditis elegans model.

In addition to their fermentable dietary fiber and the soluble ß-glucan fiber, oats have unique avenanthramides that have anti-inflammatory and antioxidant properties that reduce coronary heart disease in human clinical trials. We hypothesized that oat consumption will increase insulin sensitivity, reduce body fat, and improve health span in Caenorhabditis elegans through a mechanism involving the daf-2 gene, which codes for the insulin/insulin-like growth factor-1-like receptor, and that hyperglycemia will attenuate these changes. Caenorhabditis elegans wild type (N2) and the null strains sir-2.1, daf-16, and daf-16/daf-2 were fed Escherichia coli (OP50) and oat flakes (0.5%, 1.0%, or 3%) with and without 2% glucose. Oat feeding decreased intestinal fat deposition in N2, daf-16, or daf-16/daf-2 strains (P < .05); and glucose did not affect intestinal fat deposition response. The N2, daf-16, or sir-2.1 mutant increased the pharyngeal pumping rate (P < .05), a surrogate marker of life span, following oat consumption. Oat consumption increased ckr-1, gcy-8, cpt-1, and cpt-2 mRNA expression in both the N2 and the sir-2.1 mutant, with significantly higher expression in sir-2.1 than in N2 (P < .01). Additional glucose further increased expression 1.5-fold of the 4 genes in N2 (P < .01), decreased the expression of all except cpt-1 in the daf-16 mutant, and reduced mRNA expression of the 4 genes in the daf-16/daf-2 mutant (P < .01). These data suggest that oat consumption reduced fat storage and increased ckr-1, gcy-8, cpt-1, or cpt-2 through the sir-2.1 genetic pathway. Oat consumption may be a beneficial dietary intervention for reducing fat accumulation, augmenting health span, and improving hyperglycemia-impaired lipid metabolism.

The protective effect of Yi-Qi-Yang-Yin-Ye, a compound of traditional Chinese herbal medicine in diet-induced obese rats.

The present study was undertaken to determine the effect of Yi-Qi-Yang-Yin-Ye (Y-Q-Y-Y-Y), a compound of Traditional Chinese Herbal Medicine, on insulin resistance (IR) in the diet-induced obese rat model induced by intravenous injection with a low dose of streptozotocin and fed a high fat and high caloric diet. Y-Q-Y-Y-Y (2, 4, 8 g/kg) was administered via gavage daily for 4 weeks. The results showed that Y-Q-Y-Y-Y treatment decreased the levels of body weight, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), free fatty acid (FFA), insulin (INS) and fast blood glucose (FBG) and increased the level of high density lipoprotein-cholesterol (HDL-C) in the diet-induced obese rats. Glucose tolerance was improved in the diet-induced obese rats treated with Y-Q-Y-Y-Y as well as GIR (glucose infusion rate) in the hyperinsulinemic euglycemic clamp experiment compared to the model control rats (p < 0.01). Moreover, treatment with Y-Q-Y-Y-Y up-regulated glycogen contents in both liver and skeletal muscle and increased insulin receptor amounts on the erythrocytes surface as assessed by using (125)I-labeled auto-antibodies against insulin receptors. Taken together, our data suggested that Yi-Qi-Yang-Yin-Ye ameliorates insulin resistance in the diet-induced obese rats.

Effects of Tai Chi exercise on patients with type 2 diabetes.

This study investigated the effects of Tai Chi exercise on the levels of blood glucose, insulin and insulin receptors of patients with type 2 diabetes. Twelve subjects aged 58-75 years old (66.5 +/- 8.5 years) with type 2 diabetes participated in the study. They were trained with the protocol of Tai Chi exercise for 8 weeks. Blood glucose, serum insulin, and insulin receptor activity were measured before and after the 8-week intervention and immediately after a single bout exercise of Tai Chi after the protocol. The results showed that by 8 weeks of Tai Chi exercise, the blood glucose decreased (p < 0.05), while high- and low-affinity insulin receptor numbers (r1, r2) and low-affinity insulin receptor binding capacity (R2) increased. Serum insulin increased (p < 0.05) but was still within the normal range. After the single bout Tai Chi exercise, blood glucose, high- and low-affinity insulin receptor numbers (r1, r2), and their binding capacity (R1, R2) increased (p < 0.05), while serum insulin did not change. The 8-week Tai Chi intervention therefore showed benefits on health status of patients with type 2 diabetes.

Dietary branched-chain amino acids suppress the expression of pancreatic amylase mRNA in rats.

Regulators for pancreatic amylase were examined. Rats were fed ad libitum a 20% amino acid (AA) mixture diet (Con), a 60% AA diet (HA), a branched-chain amino acid (BCAA)-rich diet (BC), or a diet supplemented with AA other than BCAA (OA) for 7 d, or fed the Con, HA, BC diets or diets supplemented with individual BCAA. Activity and mRNA levels of pancreatic amylase in the BC and HA groups were lower than those in the Con and OA groups. Leucine and isoleucine contributed to these effects of the BC diet. The mRNA levels correlated with individual pancreatic BCAA concentrations but not with plasma insulin level. In conclusion, dietary BCAA, especially leucine and isoleucine, may reduce amylase mRNA and activity in rats.