We conclude that increased fasting proinsulin levels precede abnormalities of insulin secretion, and are an early indication of minor B-cell damage in these twins irrespective of their risk of developing diabetes.
We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr.
In animal models for type 2 diabetes the contents of preproinsulin mRNA are lowered, which might suggest that an impaired metabolism of preproinsulin mRNA contributes to the development of glucose intolerance and diabetes.
When we perturbed signalling by expressing dominant-negative forms of the receptors, FGFR1c and FGFR2b, in the pancreas, we found that that mice with attenuated FGFR1c signalling, but not those with reduced FGFR2b signalling, develop diabetes with age and exhibit a decreased number of beta-cells, impaired expression of glucose transporter 2 and increased proinsulin content in beta-cells owing to impaired expression of prohormone convertases 1/3 and 2.
Despite the Leydig cells translate human proinsulin and secrete a significant level of free C-peptide into the serum, the Leydig cell-derived insulin is not able to overcome the diabetes in different mouse models of diabetes, suggesting a lack of glucose sensing mechanisms in the Leydig cells.
The mean (SD) insulitis score was significantly reduced (1.156 [0.575] vs 2.156 [0.892] or 3.043 [0.728], P = 0.009 or <0.001), and diabetes was nearly completely prevented (1/13 vs 5/12 or 4/9, P = 0.031 or 0.013) in recipients of transduced HSCs expressing proinsulin II as compared with recipients of nontransduced HSCs or unmanipulated control.
Human proinsulin gene was transfected successfully and expressed efficiently in 293 cells, and the expression was modulated by tetracycline and its derivatives, improving the accuracy, safety, and reliability of gene therapy, suggesting that conditional establishment of artificial beta-cells may be a useful approach to develop cellular therapy for diabetes mellitus.
The results suggest that newborn children have high proinsulin and low C-peptide levels unrelated to heredity of diabetes and that the previously described elevated proinsulin level observed in older first degree relatives of diabetic subjects occurs later in life.
Peroxisome proliferator-activated receptor-gamma coactivator-1alpha activation of CYP7A1 during food restriction and diabetes is still inhibited by small heterodimer partner.
Moreover, renal KLF6 and Txnip expression increased in rats with diabetes mellitus and was inhibited by PPAR-gamma agonist treatment; however, KLF6 expression did not change in HK-2 cells exposed to PPAR-gamma agonists.
Interestingly, it also modulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and pancreatic and duodenal homeobox 1 (PDX-1).Our findings showed that <i>A. annulatum</i> and its bioactive compounds are capable of improving insulin secretion by pancreatic β-cells.This suggests that <i>A. annulatum</i> can be used as a therapeutic agent to treat diabetes.
Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor involved in the regulation of lipid metabolism, diabetes, obesity, atherogenesis and inflammation.
This novel TZD has low affinity for binding and activation of PPARγ and has insulin-sensitizing effects in mouse models of diabetes and ability to lower glucose in Phase 2 clinical trials.
We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1.
Our present study indicates a unique beneficial aspect of telmisartan: it may work as an anti-inflammatory agent against AGE by suppressing RAGE expression via PPAR-gamma activation in the liver and may play a protective role in vascular injury in diabetes.
This review highlights the roles that PPARgamma play in the regulation of gene expression associated with normal cell physiology as well as the pathophysiology of multiple diseases including obesity, diabetes and cancer.