Peroxisome proliferator-activated receptor-␥ (PPAR-␥) is a nuclear receptor that is activated by the binding of an appropriate ligand. Several studies have demonstrated that certain ligands can also induce the expression of PPAR-␥. In the present study, we examined the mechanism whereby this induction occurs by specifically addressing whether potentiation of the transactivation function of PPAR-␥ per se leads to induction of expression. We observed that thiazolidinediones, a group of insulin-sensitizing drugs, had differential effects, with troglitazone inducing protein levels of PPAR-␥, while rosiglitazone, englitazone, and ciglitazone were without effect. Similarly, the prostaglandin metabolite 15-deoxy-⌬ 12,14 -prostaglandin J 2 and the potent syn-

In addition to being the main source of energy in the human diet, starch is also used for a wide variety of industrial processes. Potato, maize, wheat and cassava are the major sources for industrial starch. While there are significant species‐dependent differences among these starches, in most cases it is necessary to chemically or physically modify the starches in order to meet the various industrial needs. The advent of molecular biology and genetic engineering has provided the requisite technologies to produce starches in planta with improved properties, which may reduce or eliminate the need for in vitro starch modification. In the last decade significant progress in our understanding of starch biosynthesis has been achieved through the use of these technologies. In this review, starch structure, functionality and use in industry are discussed. The recent discoveries in the area of starch biosynthesis are reviewed and several potential plant breeding and/or genetic engineering strategies for the modification of starch synthesis in planta are presented.

Tumor necrosis factor-alpha (TNF-alpha) mediated attenuation of insulin signaling pathway is an important cause in several disorders like obesity, obesity linked diabetes mellitus. TNF-alpha actions vary depending upon concentration and time of exposure in various cells. In the present study, the effects of long-term TNF-alpha (1 ng/ml) exposure on the components of insulin signaling pathway in HepG2 and HepG2 cells overexpressing constitutively active Akt1/PKB-alpha (HepG2-CA-Akt/PKB) have been investigated. In parental HepG2 cells, TNF-alpha treatment for 24 h reduced the phosphorylation of Akt1/PKB-alpha and GSK-3beta and under these conditions cells also showed reduced insulin responsiveness in terms of Akt1/PKB-alpha and GSK-3beta phosphorylation. TNF-alpha pre-incubated HepG2-CA-Akt/PKB cells showed lower reduction in Akt1/PKB-alpha and GSK-3beta phosphorylation and insulin responsiveness after 24 h as compared to parental HepG2 cells. We report that the long-term TNF-alpha pre-incubation in both parental HepG2 and HepG2-CA-Akt/PKB-alpha cells leads to the reduction in the levels of IRS-1 without altering the levels of IRS-2. In order to understand the reason for the differential insulin resistance in both the cell types, the effect of long-term TNF-alpha treatment on the proteins upstream to Akt/PKB was investigated. TNF-alpha pre-incubation also showed reduced insulin-stimulated Tyr phosphorylation of insulin receptor (IR-beta) in both the cell types, moreover hyperphosphorylation of IRS-1 at Ser 312 residue was observed in TNF-alpha pre-incubated cells. As hyperphosphorylation of IRS-1 at Ser 312 can induce its degradation, it is possible that reduced insulin responsiveness after long-term TNF-alpha pre-incubation observed in this study is due to the decrease in IRS-1 levels.

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Troglitazone is an oral insulin-sensitizing drug used to treat patients with type 2 diabetes. A major feature of this hyperglycemic state is the presence of increased rates of hepatic gluconeogenesis, which troglitazone is able to ameliorate. In this study, we examined the molecular basis for this property of troglitazone by exploring the effects of this compound on the expression of the two genes encoding the major regulatory enzymes of gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary cultures of rat hepatocytes. Insulin is able to inhibit expression of both of these genes, which was verified in our model system. Troglitazone significantly reduced mRNA levels of PEPCK and G6Pase in rat hepatocytes isolated from normal and Zucker-diabetic rats, but to a lesser extent than that observed with insulin. Interestingly, troglitazone was unable to reduce cAMP-induced levels of PEPCK mRNA, suggesting that the molecular mechanism whereby troglitazone exerted its effects on gene expression differed from that of insulin. This was further supported by the observation that troglitazone was able to reduce PEPCK mRNA levels in the presence of the insulin signaling pathway inhibitors wortmannin, rapamycin, and PD98059. These results indicate that troglitazone can regulate the expression of specific genes in an insulin-independent manner, and that genes encoding gluconeogenic enzymes are targets for the inhibitory effects of this drug.