Search Results

You are looking at 1 - 10 of 395 items for :

  • diabetes II x
Clear All
Free access

S Jesmin, I Sakuma, A Salah-Eldin, K Nonomura, Y Hattori and A Kitabatake

Erectile dysfunction (ED) is commonly experienced in men with diabetes mellitus. Vascular endothelial growth factor (VEGF) has been extensively documented for its pathogenic significance in different complications of diabetes. We hypothesized that expressions of VEGF, its receptors and its signaling pathway Akt may be drastically altered in diabetic penile tIssues and their alterations may modulate penile expression of the molecules that are believed to play a role in diabetic ED. Otsuka Long-Evans Fatty (OLETF) rats, a type II (non-insulin-dependent) diabetes mellitus, were used at the insulin-resistant stage of type II diabetes (20 weeks of age). We determined protein and mRNA expressions of VEGF, its receptors, Akt, nitric oxide synthase isoforms, and apoptosis-related molecules in the penis using immunohistochemistry, Western blotting, in situ hybridization, and real-time quantitative PCR analyses. The penile sections were also submitted to the Tdt-mediated dUTP nick end labeling assay for apoptosis. OLETF rats showed marked reductions in penile expression of VEGF, its two receptors and Akt. In OLETF rat penises, endothelial and neuronal nitric oxide synthase isoforms were expressed less abundantly. Furthermore, while anti-apoptotic markers, Bcl-2 and phosphorylated Bad, were down-regulated, pro-apoptotic markers, active caspase-3 and Bax, were up-regulated, resulting in the appearance of apoptotic cells in the penile tIssues of OLETF rats. The VEGF signaling system would work less well in diabetic penile tIssues as a result of the reduced expression, leading to diminished endothelial production of nitric oxide and apoptosis-related erectile tIssue damage. We propose that the abnormalities of the VEGF signaling system in the penis may play a role in the pathophysiology of diabetic ED.

Free access

Lei Yang, Hongzheng Meng and Maowei Yang

calculated relative risk based on BMD ( Yamagishi 2011 , Yamaguchi & Sugimoto 2012 , Weber et al. 2015 ). Furthermore, BMD is normal or increased rather than decreased in type II diabetes ( Hamann et al. 2012 , Yamaguchi & Sugimoto 2012 ). Advanced

Free access

Hyeon Young Park, Hye Suk Kang and Seung-Soon Im

has led to an increase in the number of people living with serious metabolic dysfunctions (e.g., diabetes) as well as cardiovascular diseases ( Monteiro & Azevedo 2010 , Han & Lean 2016 ). Cellular lipids and cholesterol are important for the

Open access

Yihong Wan and Ronald M Evans

atherosclerosis. The importance of this receptor is accentuated by the widespread use of TZDs as drugs for insulin resistance and type II diabetes. Numerous studies using mouse genetic models or synthetic PPARγ agonists have suggested that PPARγ also regulates

Free access

Carmela Santangelo, Paola Matarrese, Roberta Masella, Maria Chiara Di Carlo, Angela Di Lillo, Beatrice Scazzocchio, Elio Vecci, Walter Malorni, Riccardo Perfetti and Emanuela Anastasi

Introduction The correct balance between apoptosis and cell proliferation is a crucial factor in maintaining an appropriate mass of completely functional β-cells within the pancreatic islets. Type 2 diabetes occurs when the insulin

Free access

S Dubois, A M Madec, A Mesnier, M Armanet, K Chikh, T Berney and Ch Thivolet

activated under physiological but also pathological conditions such as inflammatory processes. During diabetes, the angiogenic answer to ischemia differs according to tissue, which is either excessive in certain organs such as the retina with

Free access

CJ Rhodes

Certain nutrients, pharmacological agents and growth factors can stimulate pancreatic beta-cell proliferation; however, mitogenic signal transduction pathways in beta-cells have not been particularly well characterized. As a model system we have focussed on characterizing the signal transduction pathways immediately downstream of the IGF-I and GH receptors in beta-cells. The original idea was to gain an idea of important elements in mitogenic signaling pathways which might then be exploited to generate a marked increase in beta-cell proliferation. Such an approach could eventually reveal a means to increase the number of human pancreatic endocrine cells in vitro, in order to obtain an abundant source of beta-cells for routine transplantation therapy of type-I diabetes. However, in the course of our studies, we have also unveiled an unexpected insight into the pathogenesis of obesity-linked type-II diabetes. It has been observed that free fatty acids inhibit glucose- and glucose-dependent IGF-I/GH-induced beta-cell proliferation. We hypothesize that a gradual accumulation of intracellular fat in beta-cells during obesity can eventually lead to an inhibition of beta-cell mass expansion and hence failure to compensate for peripheral insulin resistance, so that type-II diabetes ensues.

Free access

HJ Welters, SA Smith, M Tadayyon, JH Scarpello and NG Morgan

Chronic exposure of pancreatic beta-cells to saturated fatty acids leads to loss of viability, an effect that has been implicated in the process of beta-cell 'lipotoxicity' associated with the progression of type 2 diabetes. The mechanisms involved are unknown but recent evidence has implicated the delta isoform of protein kinase C (PKCdelta) in mediating fatty acid toxicity. We have investigated this proposition in the clonal insulin-secreting cell line, BRIN-BD11. BRIN-BD11 cells were found to undergo apoptosis when exposed to palmitate and this response was attenuated by the purportedly selective inhibitor of PKCdelta, rottlerin. However, activation of PKCdelta with the phorbol ester, phorbol-12-myristate-13-acetate (PMA), failed to promote cell death and down-regulation of PKCdelta did not prevent the cytotoxic effects of palmitate. Moreover, rottlerin remained effective as a blocker of the palmitate response in cells depleted of PKCdelta. Since rottlerin can inhibit various other kinases in addition to PKCdelta, a range of additional kinase inhibitors was also tested. Of these, only the putative Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) inhibitor, KN-62, was found to inhibit palmitate-induced cell death. However, this effect was not reproduced by a more selective pseudo-substrate inhibitor of CaM kinase II. Therefore, the present results reveal that palmitate induces cell death in BRIN-BD11 cells and suggest that this may involve the activation of a rottlerin (and KN-62)-sensitive kinase. However, it is clear that PKCdelta is not required for this response.

Restricted access

T. Sawa, S. Ohgaku, H. Morioka and S. Yano

ABSTRACT

Two insulin genes of the NON mouse, an animal model of human non-obese, non-insulin-dependent diabetes mellitus, were isolated and characterized to examine the hypothesis that these genes are structurally different from those of normal mice. The NON mouse was found to have two non-allelic insulin genes, as does the normal mouse, and no structural differences were found between the normal and NON mouse in the nucleotide sequence of the insulin gene, including that of the 5′-transcriptional regulatory region, and in the deduced amino acid sequence. There was, however, an additional 113 bp sequence and seven point mutations in a further 5′-flanking region, and three point mutations in the 3′-flanking region of the insulin II gene. We conclude that reduced expression of insulin genes in the NON mouse is not due to the structural change in the known transcriptional regulatory region, although the effect on insulin II gene expression of an additional sequence upstream of the 5′-flanking region, as the negative regulatory factor, remains to be elucidated.

Free access

PS Leung and PO Carlsson

The classical concept of the renin-angiotensin system (RAS) is that of a blood-borne cascade, whose final and bioactive product, angiotensin II, plays an important endocrine role in the maintenance of blood pressure and electrolyte as well as fluid balance. In addition to this circulating RAS, there are an increasing number of studies to suggest the existence of a local angiotensin-generating system in several tissues. The so-called tissue RAS can act locally as a paracrine and/or autocrine factor in meeting specific needs for individual tissues and it can operate, in whole or in part, independently of the circulating counterpart. Recent studies on the expression and localization of key RAS components, particularly angiotensinogen and renin, have provided solid evidence for the existence of an intrinsic, angiotensin-generating system in the pancreas. The tissue RAS has a potential role in finely regulating exocrine and endocrine functions of the pancreas such as ductal anion secretion and islet hormonal secretion. Some of these effects may be exerted via the markedly vasoconstrictive effects of RAS. Of particular interest in this context are the recent epidemiological data showing that administration of angiotensin-converting enzyme inhibitors appears to be protective against the development of diabetes in hypertensive patients. Moreover, the upregulation of pancreatic RAS has been shown to occur during chronic hypoxia. The significance of changes in pancreatic RAS could have a potential role in acute pancreatitis, islet transplantation and in different shock states, by causing a further decrease of blood perfusion in the pancreas.