Serotonin enhances the production of type IV collagen by human mesangial cells

Serotonin enhances the production of type IV collagen by human mesangial cells.BackgroundThe plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic patients is higher than that in normal subjects. Since recent reports have demonstrated the presence of 5-HT2A receptor in glomerular mesangial cells, it is possible that 5-HT may be involved in the development of diabetic nephropathy through the 5-HT2A receptor in mesangial cells. Because expansion of the glomerular mesangial lesion is a characteristic feature of diabetic nephropathy, we examined the effect of 5-HT on the production of type IV collagen by human mesangial cells.MethodsHuman mesangial cells were incubated with 5-HT with or without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or transforming growth factor-β (TGF-β) antibody. Type IV collagen mRNA and protein concentration in medium were measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. TGF-β mRNA and bioactivity in the medium were measured by Northern blot analysis and bioassay using mink lung epithelial cells, respectively.Results5-HT stimulated the production of type IV collagen by human mesangial cells, which was inhibited by ketanserin and sarpogrelate hydrochloride, 5-HT2A receptor antagonists, but not by ondansetron, a 5-HT3 receptor antagonist. 5-HT increased the bioactivities of both active and total TGF-β. However, the 5-HT-enhanced production of type IV collagen was completely inhibited by an anti-TGF-β antibody. Furthermore, a PKC inhibitor, calphostin C, inhibited the 5-HT-induced increase in type IV collagen secretion, and the activity of membrane PKC was increased by 5-HT. Phorbol ester activated type IV collagen production as well as active and total TGF-β. Calphostin C completely inhibited the 5-HT-enhanced activity of active TGF-β, but did not inhibit exogenous TGF-β-induced increase in type IV collagen secretion.ConclusionsOur results suggest that 5-HT-enhanced production of type IV collagen by human mesangial cells is mediated by activation of PKC and subsequent increase in active TGF-β activity

What is artificial endocrine pancreas? Mechanism and history

The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedside-type artificial endocrine pancreas is now available in Japan: STG-22 (Nikkiso Co. Ltd., Japan). In the insulin infusion algorithm, insulin is infused on the basis of its proportional and derivative actions, to blood glucose concentrations with a constant time delay. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus, but also as an elegant research tool for investigating the pathophysiology of the disease, by using the euglycemic hyperinsulinemic glucose clamp technique. The wearable type of closed-loop system has been developed recently. The breakthrough is the establishment of a needle-type glucose sensor. The development of closed-loop glycemic control systems that enable long-term physiological regulation has focused on implantable devices. Much effort has been expended to realize these devices

IMPLANTABLE GLUCOSE SENSOR - PROBLEMS AWAITING SOLUTIONS FOR LONG-TERM CLINICAL APPLICATION

We developed an indwelling, exchangeable and disposable glucose sensor. For preserving excellent in vivo characteristics and extending sensor longevity, the most crucial points are the elegant membrane design and the software backup system. We have developed a band path filter, which was effective in eliminating several types of electrical noises evoked by muscle works or electrical disturbances. The new glucose sensor covered by alginate-polylysine-alginate membrane as a biocompatible one could preserve the sensor activity for 14 days after implantation in subcutaneous tissue of normal dogs. These data indicated that further improvements in membrane design might augment the long-term clinical applicability of glucose sensor

MEMBRANE DESIGN OF GLUCOSE SENSOR FOR LONG-TERM CLINICAL USE - APPLICATION OF ALGINATE-POLYLYSINE-ALGINATE MEMBRANE -

For extending sensor longevity, we coated the alginate-polylysinealginate membrane on the needle-type glucose sensor. The glucose sensor could determine the whole blood glucose concentration directly and preserve the sensor activity for 14 days after implantation. These data indicated that further improvements in membrane design might augment the long-term clinical applicability of glucose sensor