ABSTRACT
Existing data show that C-peptide (CP) prevents or ameliorates diabetes-related complications mainly by improving microcirculation and perhaps metabolism. Although effects of CP on muscle glucose consumption are relatively well studied, its effects on adipose tissue, a key organ involved in metabolism, are not well known. Therefore, the aim of this study was to examine the effects of CP on basal and stimulated lipolysis and glucose consumption in rat retroperitoneal (RP) adipose tissue, using an EX-VIVO organ culture setting. The RP adipose tissue was excised from adult male rats, minced and subjected to EX-VIVO culture for 24 h. The tissue fragments were then weighted and distributed into a 24-well culture plate. The wells were left untreated (basal) or treated with insulin or isoproternol (ISO, stimulated) and incubated in the absence or presence of CP, insulin or a combination of the both peptides. Levels of lipolysis and tissue glucose consumption were determined by glycerol and glucose concentrations measurement in the infranatant conditioned media collected from each well. The CP, like insulin, induced an insignificant reduction in basal lipolysis. While insulin significantly reduced the ISO-stimulated lipolysis, CP was ineffective. Tissue glucose consumption was significantly stimulated by insulin, but was not affected by CP. However, in the presence of CP, inhibitory effect on ISO-stimulated lipolysis and stimulatory effect on glucose consumption of insulin were significantly diminished. Our data suggest that CP may conditionally modulate certain metabolic actions of insulin in RP adipose tissue. These modulations may contribute to fine-tuning of body metabolism under physiologic or pathologic conditions.
Subject(s)
Adipose Tissue/drug effects , C-Peptide/pharmacology , Glucose/metabolism , Lipolysis/drug effects , Adipose Tissue/metabolism , Animals , Cell Survival/drug effects , Cells, Cultured , Drug Evaluation, Preclinical , Endothelial Cells/drug effects , Endothelial Cells/physiology , Insulin/pharmacology , Male , Rats , Rats, Sprague-Dawley , Stromal Cells/drug effects , Stromal Cells/physiologyABSTRACT
Type-1 diabetes (T1D) is a metabolic disorder associated with massive reduction in mass of adipose tissue. Measuring cell diameter, an index of fat metabolism, we determined depot-specific alterations in weight of adipose tissue, fat cell diameter and size heterogeneity and distribution at 5 depots in streptozotocin (STZ)-induced diabetic rats. T1D was induced by a single injection of STZ. Seven days after the injection, fat depots were isolated, weighted, washed and maintained in tissue culture medium. Using a microscope equipped with calibrated micrometer, cell diameter as well as size distribution pattern and heterogeneity of adipocytes were determined in fresh tissue slices of subcutaneous (SC), proximal epididymal (PE), distal epididymal (DE), perirenal (PR) and retroperitoneal (RP) fat depots. The T1D induced marked reductions in fat mass and mean of fat cell diameter at all depots. The most affected depot was the SC. With the exception of PE, adipocytes at all depots showed significant increases in size heterogeneity. The effect of the diabetes on mean fat cell diameter and size heterogeneity was minimal at PE depot. Depots with similar cell size distribution pattern exhibited similar fat mass reduction. However, the DE depot with a unique cell size distribution pattern showed a fat mass reduction similar to that of PE and PR depots. These data indicate that T1D induces a massive fat mass reduction in a reasonably depot-specific manner and that the fat depots close to survival organs are less vulnerable to fat mobilization. Moreover, peculiar disagreement between cell size distribution and heterogeneity as well as the level of fat mass reduction at DE and PE depots suggests that not only cell size and heterogeneity but also local factors may play roles in depot-specific fat mobilization.
