Correlation of insulin resistance, beta cell function and insulin sensitivity with serum sFas and sFasL in newly diagnosed type 2 diabetes.
ABSTRACT Pancreatic beta cell dysfunction and reduced insulin sensitivity are fundamental factors associated with glucotoxicity, lipotoxicity and oxidative stress in type 2 diabetic patients (T2DM). Diabetic milieu can induce apoptosis in several types of cells. The aim of present study was to compare circulating soluble apoptotic markers (sFas and sFas-L) with HOMA-IR, HOMA-%S, HOMA-%B in the serum of newly diagnosed T2DM and healthy subjects. For this study, 94 T2DM and 60 healthy subjects were enroled and evaluated for various parameters. Biochemical quantifications were performed with Syncron CX5 auto-analyzer. The levels of serum sFas-L, TNF-α and IL-6 were estimated by flowcytometry. The fasting serum insulin and sFas quantified by ELISA. HOMA-IR, HOMA-%S and HOMA-%B were calculated with HOMA calculator v2.2.2. The levels of TC, TG, LDL-C, VLDL-C were augmented and HDL declined significantly (P < 0.001) in diabetics. The levels of serum insulin, TNF-α, IL-6, sFas, HOMA-IR were raised (P < 0.001) and sFas-L, HOMA-%S and HOMA-%B were decreased significantly (P < 0.001) in T2DM subjects than healthy. In diabetics, serum sFas was positively correlated with HOMA-IR (r = 0.720, P < 0.001) and negatively with HOMA-%B (r = -0.642, P < 0.001) significantly while serum sFasL was negatively correlated with HOMA-IR (r = -0.483, P < 0.001) and positively with HOMA-%B (r = 0.466, P < 0.001) significantly. Further, the multivariate stepwise regression analysis shows that HOMA-IR contributes significantly to the variance of sFas and sFasL. Our findings suggest that the pancreatic beta cell dysfunction along with increased insulin resistance appears to be associated with apoptotic markers.
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ABSTRACT: Post-transplant diabetes mellitus represents an important complication of prolonged immunosuppressive treatment after solid organ transplantation. The immunosuppressive toxicity, responsible for a persistent impairment of glucose metabolism in pancreatic islet-transplanted patients, is mainly attributed to calcineurin inhibitors and steroids, while other immunosuppressive molecules (azathioprine and mycophenolic acid, MPA) are considered not to have a toxic effect. In the present study, in vitro effects of MPA have been investigated in mouse beta-cell lines (βTC-1 and βTC-6) and in purified human pancreatic islets. βTC-1, βTC-6, and human pancreatic islets were exposed to various concentrations of MPA for different times. Consequently, we evaluated the viability, the induction of apoptosis, the glucose-stimulated insulin secretion, and the expression of β-cell function genes (Isl1, Pax6, Glut-2, glucokinase) and apoptosis-related genes (Bax and Bcl2). βTC-1, βTC-6, and human islets treated, respectively, for 48 and 72 h with 15-30 nM MPA showed altered islet architecture, as compared with control cells. We observed for βTC-1 and βTC-6 almost 70% reduction in cell viability; three to sixfold induction of TUNEL/apoptotic-positive cells quantified by FACS analysis. A twofold increase in apoptotic cells was observed in human islets after MPA exposure associated with strong inhibition of glucose-stimulated insulin secretion. Furthermore, we showed significant down-regulation of gene expression of molecules involved in β-cell function and increase rate between Bax/Bcl2. Our data demonstrate that MPA has an in vitro diabetogenic effect interfering at multiple levels with survival and function of murine and human pancreatic β-cells.Acta Diabetologica 01/2012; · 4.63 Impact Factor
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ABSTRACT: Diabetics die from cardiovascular disease at a much greater rate than nondiabetics. Cardiac autonomic imbalance predicts increased cardiovascular risk and mortality. We studied the relationship between cardiac autonomic imbalance and adipose tissue-derived inflammation in newly diagnosed and established type 2 diabetes. Non-diabetics, newly diagnosed diabetics, and established diabetics were included. Anthropomorphic and biochemical measurements were obtained, and insulin resistance was approximated. Cardiac autonomic function was assessed using conventional measures and with power spectral analysis of heart rate. Heart rate variability was reduced in all diabetics. Interleukin-6 was higher in diabetics, as was the high molecular weight adiponectin-to-leptin ratio. Interleukin-6 correlated negatively with measures of autonomic balance. Ratios of adiponectin to leptin correlated positively with measures of autonomic balance. Cardiac autonomic imbalance and inflammation occur early in diabetes and are interrelated. Cardiac autonomic imbalance correlates with the adipose tissue-derived inflammation seen early in type 2 diabetes.Experimental Diabetes Research 01/2012; 2012:878760. · 1.89 Impact Factor
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ABSTRACT: Diabetes mellitus (DM), a growing health problem globally, has reached epidemic proportions in India. Recently, Fas-mediated apoptosis has been proposed as a causative factor responsible for neuronal degeneration in diabetic polyneuropathy (DPN), but there are very few studies to show association of serum soluble Fas ligand (sFasL) level with severity of neuropathy. The aim of this study was to investigate whether serum sFasL, a transmembrane glycoprotein involved in apoptosis, has any association with severity of peripheral neuropathy in Type 2 DM. The study was conducted in Department of Physiology in collaboration with Department of Endocrinology, IPGME&R. sFasL levels in serum were assessed using ELISA method in healthy individuals (n = 16), newly diagnosed diabetic controls (n = 16) without any complications, and in DPN cases (n = 33) with predominant neuropathy only. All subjects underwent both electrodiagnostic procedures and vibration perception threshold (VPT) for quantitative assessment of the severity of neuropathy. Using nerve conduction studies, amplitudes, velocities, and latencies of both sensory and motor nerves were recorded. In DPN patients, concentration of sFasL levels (87.53 ± 3.49) was significantly decreased (P < 0.0001) not only when compared with normal controls (225.30 ± 2.97) but also when compared with diabetic patients without any complication (161 ± 3.63). Moreover, the concentration of sFasL is significantly (P < 0.0001) associated with the severity of neuropathy both by VPT and nerve conduction velocity (NCV). Fas-mediated apoptosis is involved in Type 2 DM and might be associated with the severity of polyneuropathy.Indian journal of endocrinology and metabolism. 12/2012; 16(Suppl 2):S465-7.