It is widely acknowledged that activation of the renin-angiotensin system impairs insulin sensitivity. Pharmacological inhibition of the (pro)renin receptor-dependent system has shown beneficial effects in diabetic nephropathy, retinopathy and hypertensive cardiac damage in animal models. Previously, we showed that fructose feeding stimulated nonproteolytic activation of prorenin and subsequent...

By differential hybridization screening of a cDNA library derived from insulin-stimulated cells, we selected a clone which hybridized to an mRNA species that rapidly accumulated in response to insulin. The insert from this clone encoded a putative polypeptide of Mr 33,600, pI 11.2; because the protein was enriched in proline residues (14.4 mol %) and contained three Pro-Pro-Pro-Pro repeats, we ...

Milk derived tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) have shown promise as anti-hypertensive agents due to their inhibitory effects on angiotensin converting enzyme (ACE). Due to the key inter-related roles of hypertension, chronic inflammation and insulin resistance in the pathogenesis of metabolic syndrome, there is growing interest in investigating established anti-hypertensive a...

Broad nervous circuits originate from the hypothalamic arcuate nucleus project to many parts of the brain which are related to pain perception. Insulin receptors have been found in the arcuate nucleus. Since nociception may be affected in type 1 diabetes, the present study aimed to investigate the intra-arcuate nucleus insulin role in pain perception in STZ-induced diabetic and healthy rats. Fo...

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro)GIP. Young adult ob/ob mice re...

Peroxisome Proliferator Activated Receptors (PPAR) are members of the nuclear receptor superfamily of ligand activated transcription factor consisting of 3 subtypes PPARα , PPARβ and PPARγ. PPARγ plays an important role in adipocyte differentiation and it regulates lipid metabolism as well as insulin sensitivity. Of the 3 isoforms of PPARγ, PPARγ2 are expressed in adipose tissue. Genomic DNA wa...

If an adipocyte is programmed to secrete insulin, then the insulin released may amplify the insulin action by an autocrine manner. To examine this hypothesis in vitro, we investigated the effects of expressing the preproinsulin gene in 3T3L1 adipocytes on (pro)insulin release and glucose uptake. The human preproinsulin gene was transferred into 3T3L1 adipocytes by infecting the cells with recom...

BACKGROUND: The liver has been suggested as a suitable target organ for gene therapy of Type 1 diabetes. However, the fundamental issue whether insulin-secreting hepatocytes in vivo will be destroyed by the autoimmune processes that kill pancreatic beta cells has not been fully addressed. It is possible that the insulin secreting liver cells will be destroyed by the immune system because hepato...

Adiponectin exerts cardiovascular protective actions, although some studies have shown the opposite. In hemodialysis, obese subjects display lower mortality rates despite hypoadiponectinemia, while higher adiponectin concentrations correlate with an elevated cardiovascular risk in nonobese subjects. The aim of the study is to suggest that adiponectin level variations are associated with differe...