| 1. |
|
|
| 2. |
- Barbu, Andreea, et al.
(författare)
-
Pref-1 and adipokine expression inadipose tissues of GK And Zucker rats
- 2009
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 299:2, s. 163-171
-
Tidskriftsartikel (refereegranskat)abstract
- In view of the central role of preadipocyte factor-1, adiponectin and leptin in white adipose tissue function, the aim of the present study was to analyze the mRNA expression of these proteins and of the inflammatory markers interleukin-6 and tumor necrosis factor-α in visceral and subcutaneous fat pads of rats with different metabolic disorders. We demonstrated highly divergent expression of preadipocyte factor-1, upregulated expression of adiponectin, interleukin-6 and TNF-α mRNA in adipose tissues of the diabetic Goto Kakizaki rat compared to the obese Zucker rat. This was correlated to an increased number of large adipocytes and serum levels of adiponectin. Furthermore, in all four strains studied (as above plus Wistar Furth and Zucker Lean), significant heterogeneity was evident in adipokine expression within specific adipose tissues previously defined as belonging to the visceral or subcutaneous fat depots. These results suggest that significantly increased levels of inflammation and redistribution of adipocyte size are mechanisms contributing to the development of type 2 diabetes in the GK rat.
|
|
| 3. |
|
|
| 4. |
- Blixt, Martin, 1977-, et al.
(författare)
-
Suppression of bank vole pancreatic islet function by proinflammatory cytokines
- 2009
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 305:1-2, s. 1-5
-
Tidskriftsartikel (refereegranskat)abstract
- Bank voles kept in captivity may develop diabetes. We recently characterized beta-cell function of pancreatic islets from normal and glucose intolerant/diabetic bank voles. These animals had features of both human type 1 and type 2 diabetes. Cytokines may impair β-cell function in both types of diabetes. Presently, we studied how pancreatic islets isolated from normal, i.e. glucose tolerant bank voles are affected by proinflammatory cytokines in vitro. Islets were exposed to hIL-1β (25U/ml) alone or in combination with hTNF-α (1000U/ml)+mIFN-γ (1000U/ml) for 48h, whereupon islet functions were assessed. Cytokines markedly reduced insulin gene expression and the (pro)insulin biosynthesis rate, which was accompanied by a profound depletion of the islet insulin content. The cytokines did not affect the culture medium insulin accumulation and the glucose oxidation rate, but caused a modest increase in medium nitrite, an indicator of nitric oxide (NO) generation. Cytokine-induced decrease in islet insulin content was not prevented by the preferential inducible NO synthase inhibitor aminoguanidine. These findings suggest that the reduction in islet insulin content is not attributed to enhanced exocytosis or related to altered glucose metabolism, but is rather due to a decline in insulin production. The suppressive effects of islet functions elicited by cytokines seem to be mediated by an NO-independent mechanism. In relation to previous studies on cytokine effects on islets from various species, the bank vole islets show a pattern which more resembles human islets than rat or murine islets.
|
|
| 5. |
- Bruun, JM, et al.
(författare)
-
Sulfatide increases adiponectin and decreases TNF-alpha, IL-6, and IL8 in human adipose tissue in vitro
- 2007
-
Ingår i: Mol Cell Endocrinol. - : Elsevier BV. ; 263:1-2, s. 142-148
-
Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is associated with decreased levels of the glycosphingolipid sulfatide, as well as a state of low-grade inflammation. Sulfatide is reported to have anti-inflammatory properties in other cell-types. In the present study, the effects of sulfatide on adipokine (adiponectin, TNF-alpha, IL-6, and IL-8) production in human adipose tissue (AT) was investigated in vitro. Isolated human adipocytes and AT cultures were incubated with sulfatide isolated from pig brain [sulfatide containing a variety of fatty acids or isoforms of sulfatide with defined, saturated fatty acids with 16 (C16:0) or 24 (C24:0) carbon atoms]. Adiponectin production was increased 50-80%, by all sulfatide preparations. Only the C16:0 isoform decreased TNF-alpha, IL-6, and IL-8 production 20-30%. The C16:0 sulfatide has been shown to activate potassium channels in beta-cells, and glibenclamide, an ATP-sensitive K(+)-(K(ATP)) channel blocker, reversed the C16:0-induced decrement in stimulated TNF-alpha, IL-6, and IL-8 release in adipocytes. Glibenclamide on its own was without effect on the production of adiponectin, TNF-alpha, IL-6, and IL-8. In conclusion, this study shows that, sulfatide exerts anti-inflammatory effects in human adipocytes and AT in vitro. Accordingly, the reported low serum levels of sulfatide in patients with type 2 diabetes might be of importance in relation to the chronic low-grade inflammatory state found in this disease.
|
|
| 6. |
- Dekker Nitert, Marloes, et al.
(författare)
-
IGF-I/insulin hybrid receptors in human endothelial cells
- 2005
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 229:1-2, s. 31-37
-
Tidskriftsartikel (refereegranskat)abstract
- Vascular complications are common in diabetes. IGF-I receptors (IGF-IR) and insulin receptors (IR) in endothelial cells might respond to altered levels of IGF-I and insulin, resulting in altered endothelial function in diabetes. We therefore studied IGF-IR and IR gene expression, ligand binding, receptor protein, and phosphorylation in human umbilical vein endothelial cells (HUVEC). IGF-IR mRNA was more abundant than IR mRNA in freshly isolated HUVEC (IGF-IR/IR ratio 7.1 +/- 1.5) and in cultured HUVEC (ratio 3.5 +/- 0.51). Accordingly, specific binding of (125)I-IGF-I (0.64 +/- 0.25%) was higher than that of (125)I-insulin (0.25 +/- 0.09%). Protein was detected for both receptors and IGF-I/insulin hybrid receptors. IGF-IR phosphorylation was stimulated by 10(-10) to 10(-8) M IGF-I. IR were activated by 10(-9) to 10(-8) M insulin and IGF-I. We conclude that HUVEC express more IGF-IR than IR, and also express hybrid receptors. Both IGF-I and insulin phosphorylate their own receptors but only IGF-I seems to phosphorylate hybrid receptors.
|
|
| 7. |
- Fred, Rikard G., et al.
(författare)
-
The importance of RNA binding proteins in preproinsulin mRNA stability
- 2009
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 297:1-2, s. 28-33
-
Forskningsöversikt (refereegranskat)abstract
- A dynamic production of insulin is necessary for proper glucose homeostasis. In order to generate enough insulin available for exocytosis in response to the demands of the organism, the level of preproinsulin mRNA in the pancreatic beta-cell needs to fluctuate. 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. Thus, it is of importance to understand the mechanisms by which preproinsulin mRNA levels are regulated. Although extensively studied, there are aspects of the regulation of insulin gene expression that still remain enigmatic. Our understanding of insulin gene transcription has improved considerably the last 20 years, but less effort has been invested into the control of preproinsulin mRNA stability. The preproinsulin mRNA has a long half-life and changes in preproinsulin mRNA stability, induced by glucose, are likely to be regulated through specific mechanisms. Recent findings indicate that the polypyrimidine tract-binding protein (PTB), also named hnRNP I, by binding to the 3'-UTR (untranslated region) of the preproinsulin mRNA molecule, stabilizes the messenger, thereby participating in the glucose-induced increase in preproinsulin mRNA. This review will focus both on recent findings pertinent to PTB function in general, and on the specific role of PTB on the production of insulin in beta-cells. We will also discuss the putative co-operativity between PTB and other proteins in the control of preproinsulin mRNA stability, and review beta-cell signaling events that may control the mRNA stabilizing effect of PTB.
|
|
| 8. |
- Gao, Ru, et al.
(författare)
-
Maturation of in vitro-generated human islets after transplantation in nude mice
- 2007
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 264:1-2, s. 28-34
-
Tidskriftsartikel (refereegranskat)abstract
- The long-term function of human pancreatic islet grafts may depend on the neogenesis of beta cells from epithelial precursors within the grafted tissue. We have developed an in vitro model for human islet neogenesis. In this study, we have investigated the morphological signs of maturation in cultivated human islet buds (CHIBs) before and after transplantation. Clusterin is a molecule associated with beta-cell differentiation in rodents. In adult human islets, clusterin expression was located only in alpha- and PP-cells, but in CHIBs and human fetal islets, it was distributed in all four types of endocrine cells. Some immature endocrine cells in the CHIBs co-expressed insulin and glucagon. After transplantation, CHIBs became mature with one type of hormone per endocrine cell, and clusterin expression became restricted in alpha-cells. Cells co-expressing endocrine markers and cytokeratin 19, as a sign of ductal to endocrine cell transition, were frequently detected in both fresh islets and CHIBs after transplantation. We conclude that clusterin may be involved in the development of islets, and the in vitro-derived islets become mature after transplantation into nude mice. Ductal cell differentiation into endocrine cells may be an important factor in sustaining the long-term function of islet transplants.
|
|
| 9. |
|
|
| 10. |
|
|
