- The Effects of Uncoupling Protein 3 Overexpression on Glucose Metabolism in OLETF Rats in Vivo and Cultured Skeletal Muscle Cells in Vitro.
-
Jeong Hee Han, Hye Seon Park, Jung Min Koh, Ha Young Kim, Ho Kyung Kang, In Kyu Lee, Joong Yeol Park, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee
-
Korean Diabetes J. 2001;25(6):460-468. Published online December 1, 2001
-
-
-
 Abstract
 PDF
- BACKGROUND
UCP3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. METHODS: An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus- UCP3 (UCP3 group) and others were injected with the adenovirus (control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C12 cells transfected with ether an adenovirus or the adenovirus-UCP3. RESULTS: The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. CONCLUSION: Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism.
- Effects of Free Fatty Acids on Glutathione Redox Status in Cultured Endothelial Cells.
-
Joong Yeol Park, Chul Hee Kim, Yun Ey Chung, Hong Kyu Kim, Young Il Kim, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee
-
Korean Diabetes J. 1998;22(3):262-270. Published online January 1, 2001
-
-
-
Abstract
PDF
- BACKGROUND
Although plasma free fatty acids (FFA) are frequently elevated in diabetes mellitus, its role in the pathogenesis of diabetic vascular complications has not been well investigated. Recent stuclies reported that FFA may cause endothelial dysfunction through an enhancement of oxidative damage by decreasing glutathione redox cycle, an important anti-oxidant defense system in endothelial cells. In this study, we examined the effects of increased availability of FFA on intracellular glutathione redox cycle. METHODS: Bovine pulonary endothelial cells were exposed to 90 umol/L linoleic acid with or without 0.1 mM 2-bromopalmitate, an inhibitor of mitochondrial fatty acid oxidation, for 6hr. Components of the glutathione redox cycle such as total glutathione, reduced glutathione(GSH) and oxidized glutathione(GSSG) concentrations were measured by HPLC. RESULTS: Total glutathione concentration in cultured endothelial cells exposed to linoleic acid was significantly lower than that in control cells (10.8+ 0.5 vs 14.1+0.8 umol/g protein, P<0.05). Linoleic acid significantly decreased GSH concentrations (10.5+0.4 vs. 13.8+0.5 pmol/g protein, P<0.05) and the ratio of GSH/GSSG(26.3+1.3 vs. 47.0+2,1, P<0.05). Compared to cells exposed linoleic acid alone, total glutathione(13.5+0.5umol/g protein, P<0.05) and GSH concentration(13.2+0.4 pmol/g protein, P<0.05) significantly increased in cells treated with 2-bromopalmitate and linoleic acid. The ratio of GSH/GSSG in cells treated with 2-bromopalmitate and linoleic acid was higher th.an that in cells exposed to linoleic acid alone(44.1+1.3, P<0.05). CONCLUSION: Increased provision of FFA resulted in a derangement of glutathione redox cycle in cultured endothelial cells, which appears to be related to an increase in mitochondrial FFA oxidation. These results suggested that FFA can increase the risk of diabetic vascular complications.
- Effects of Free Fatty Acid on Insulin Secretion in Cultured Rat Pancreatic Islets.
-
Hong Kyu Kim, Young Il Kim, Chul Hee Kim, Joong Yoel Park, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee
-
Korean Diabetes J. 1997;21(4):381-387. Published online January 1, 2001
-
-
-
Abstract
PDF
- BACKGROUND
It has been recently suggested that enhanced fat oxidation is responsible for the abnormal insulin secretory pattern in non-insulin-dependent diabetes mellitus. This study was undertaken to assess the effect of chronic exposure of pancreatic islets to free fatty acid on insulin secretion. METHODS: Rat pancreatic islets were cultured in various concentrations of glucose(5.5, 11, 27 mM) for 48 hrs with or without addition of free fatty acid(90 upM linoleic acid), and the basal and glucose-stimulated insulin secretion were measured. The effect of fatty acid oxidation inhibitor(2-bromopalmitate) was also tested. RESULTS: Islets cultured in high glucose concentrations showed a marked increase in basal insulin secretion. Free fatty acid stimulated the basal insulin secretion in islets cultured at 5.5 or 11 mM glucose, but no additional effect was seen in islets eultured at 27 mM glucose. In contrast, glucose-stimulated insulin secretion was decreased in islets cultured in high glucose media. Exposure to free fatty acid exerted an additive inhibitory effect on glucose-induced insulin secretion in islets cultured at 5.5 or 1 1 mM glucose, but not in islets cultured at 27M glucose, An inhibitor of fatty acid oxidation, 2-bromopalmitate, prevented the fatty acid-induced changes in both basal and glucosestimulated insulin secretion. CONCLUSION: These results showed that longterm exposure of pancreatic islets to free fatty acid altered the dynamics of insulin secretion, probably through a glucosefatty acid cycle.
- The oxidative modification of hepatic intracellular proteins in the streptozotocin-induced diabetic rats.
-
Yeon Jin Jang, Jae Dam Lee, Hyoung Sup Park
-
Korean Diabetes J. 1993;17(2):175-182. Published online January 1, 2001
-
-
-
Abstract
PDF
- No abstract available.
|
KDA
