Transient receptor potential cation channel 6 deficiency leads to increased body weight and metabolic dysfunction.

Transient receptor potential cation channel 6 (TRPC6), a member of the TRPC family, is expressed in the hypothalamus and modulates cell Ca2+ influx. However, the role of TRPC6 in controlling metabolic and cardiovascular functions under normal conditions has not been previously determined. Thus the impacts of TRPC6 deletion on energy balance, metabolic, and cardiovascular regulation as well as the anorexic responses to leptin and melanocortin 3/4 receptor (MC3/4R) activation were investigated in this study. Extensive cardiometabolic phenotyping was conducted in male and female TRPC6 knockout (KO) and control mice from 6 to 24 wk of age to assess mechanisms by which TRPC6 influences regulation of energy balance and blood pressure (BP). We found that TRPC6 KO mice are heavier with greater adiposity, are hyperphagic, and have reduced energy expenditure, impaired glucose tolerance, hyperinsulinemia, and increased liver fat compared with controls. TRPC6 KO mice also have smaller brains, reduced proopiomelanocortin mRNA levels in the hypothalamus, and impaired anorexic response to leptin but not to MC3/4R activation. BP and heart rate, assessed by telemetry, were similar in TRPC6 KO and control mice, and BP responses to air-jet stress were attenuated in TRPC6 KO mice despite increased body weight and metabolic disorders that normally raise BP and increase BP responses to stress. Our results provide evidence for a novel and important role of TRPC6 in controlling energy balance, adiposity, and glucose homeostasis, which suggests that normal TRPC6 function may be necessary to link weight gain and hyperleptinemia with BP responses to acute stress.

Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.

BACKGROUND AND OBJECTIVES: Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4 ± 15.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters. RESULTS: Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel.FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], P<0.001, and 39.4 ± 10.1% versus 27.2 ± 11.5%, P=0.002, respectively), lower IGFBP-1 (8.2 ± 7.2 versus 21.0 ± 16.3 ng/ml, P=0.002), but similar glucose absorption and small-solute transport compared with patients without insulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0.82, P<0.001). CONCLUSIONS: Insulin resistance in nondiabetic peritoneal dialysis patients is associated with obesity and LAR independent of glucose absorption and small-solute transport status. Fast transport status was not associated with higher likelihood of obesity or insulin resistance.

The relationship between human plasma leptin levels and obesity, plasma glucose as well as insulin concentrations / 中国糖尿病杂志

Objective To investigate the relationship between plasma leptin levels and obesity,plasma glucose as well as insulin concentrations.Methods Fasting plasma leptin concentrations were measured with IRMA in 171 cases (including 84 type 2 DM,36 IGT,51 NGT;90 men,81 women),and oral glucose tolerance test was done in every case to measure plasma glucose and insulin concentrations.Height,body weight were measured to calculate body mass index (BMI).Results Fasting plasma leptin levels are correlated with BMI( r=0.6772,P

The relationship between serum Leptin concentration and insulin resistance in type 2 diabetes / 中国实用内科杂志

Objective To investigate the relationship between serum Leptin levels and insulin resistance.Methods During 2001-10~2002-08 fasting serum Leptin concentrations were measured with RIA in 196 cases(including 118 type 2 diabetes,78 controls),and height,body weight were measured to calculate body mass index(BMI).Results HbA_1c,SBP,TG,Leptin were correlated with ISI,Leptin concentration were higher in type 2 diabetes than in controls;Leptin concentration was significantly increased in obese subjects,whereas in type 2 diabetes serum Leptin concentration had no significant difference between obese subjects and non-obese subjects.Conclusion Most of obeses subjects have insulin resistance,whether obesity or not,the patients type 2 diabetes have some kind of insulin resistance.