leptin and Primate-Diseases

Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients. This protein possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys (Macaca mulatta), which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and diabetic monkeys as in humans. Prospective longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes. Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake (M rate). The plasma levels of adiponectin were significantly correlated to M rate (r = 0.66, P < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the progression of insulin resistance. No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance.

Topics: Adiponectin; Adipose Tissue; Amino Acid Sequence; Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Disease Progression; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Macaca mulatta; Male; Molecular Sequence Data; Obesity; Organ Size; Primate Diseases; Proteins; Sequence Alignment; Sequence Homology, Amino Acid

We have cloned the rhesus monkey obese cDNA and have analyzed its expression in monkeys with a wide range of body weights (lean to very obese) and with or without non-insulin-dependent diabetes mellitus to examine the relationship of ob gene expression to obesity and non-insulin-dependent diabetes mellitus. The sequence of monkey ob protein, excluding the signal peptide, showed 91% identity with the human protein. We observed a significant correlation between the level of ob mRNA and body weight. We also found a significant relationship between ob mRNA and fasting plasma insulin concentration; however, insulin stimulation during a 100-140-min euglycemic/hyperinsulinemic clamp did not result in any changes in ob mRNA levels. Circulating levels of the ob gene product leptin were also significantly correlated with body weight. These results show that ob gene expression is related to body weight and is not acutely regulated by insulin.

Topics: Amino Acid Sequence; Animals; Base Sequence; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; DNA, Complementary; Gene Expression Regulation; Humans; Hyperinsulinism; Leptin; Macaca mulatta; Mice; Molecular Sequence Data; Obesity; Organ Specificity; Primate Diseases; Protein Biosynthesis; Protein Sorting Signals; Proteins; Rats; Regression Analysis; RNA, Messenger; Sequence Homology, Amino Acid; Transcription, Genetic