• BMB Reports
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• v.55 no.9
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• pp.453-458
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• 2022

Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.818-823
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• 2011

Recently, we showed that green tea extract (GTE) markedly lowers the intestinal absorption of $^{14}C$-benzo[a]pyrene ($^{14}C$-BaP) and enhances its secretion into the biliary route, suggesting a protective role for GTE against body burden. These findings indicate that green tea could be used as an effective dietary means against the toxicity of BaP. The present study, therefore, was designed to investigate if green tea intake could affect the tissue distribution and deposition of $^{14}C$-BaP in rats. Male Sprague-Dawley rats had free access to a nutritionally adequate AIN-93G diet and deionized water. At ~340 g of weight, the rats were injected intraperitoneally with 27.4 kBq of [4-$^{14}C$]-BaP and 5.0 mg of BaP dissolved in $300\;{\mu}L$ of olive oil and then assigned randomly to the following two groups: one group (GTE) of rats was fed the AIN-93G diet with GTE via drinking water at approx. 4.7 mg of catechins/d, whereas the other was fed the same diet but without GTE (control). At 4 wk of dietary treatment with GTE, animals were euthanized and heart, liver, brain, spleen, kidney, retroperitoneal fat, testis, and epididymal fat were collected, weighed, and analyzed for tissue $^{14}C$-BaP. Both the control and GTE groups continuously gained weight throughout the study, but there was no significant difference between the groups. No significant differences were observed in the weights of heart, liver, brain, spleen, kidney, retroperitoneal fat, testis, and epididymal fat. However, the radioactivities of $^{14}C$-BaP, expressed in dpm/g, were significantly lower in the heart, liver, brain, spleen, and epididymal fat of rats receiving GTE as compared to their respective controls. These data indicate that green tea intake markedly lowers tissue accumulation of $^{14}C$-BaP. Taken together, these findings suggest that the decreased tissue levels of BaP by GTE intake may be associated with lowered intestinal absorption of BaP and its enhanced secretion into the bile.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.2
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• pp.174-180
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• 2002

Purpose: Ursodeoxycholic acid (UDCA) is known to decrease hepatic injury by promoting the biliary secretion of retained toxic endogenous bile acids in hepatobiliary diseases complicated by total parenteral nutrition (TPN). However, most studies have focused on treatment for complications after TPN. We investigated the preventive role of early administration of UDCA in TPN-induced hepatobiliary complications by a randomized, double-blind, placebo-controlled trial. Methods: Between May 2000 and May 2002, thirteen patients, who were given TPN more than 10 days in the hospital, were assigned randomly to two groups. One was the case group (7 patients) who were given UDCA simultaneously with TPN regimen, and the other, the control group (6 patients) who were given placebo. Their age ranged from 1 day to 13 years. They were affected with diseases impossible for enteral nutrition, such as prematurity, cerebral palsy, chronic diarrhea, anorexia nervosa, pancreatitis, and cyclic vomiting. The duration of TPN ranged from 10 to 70 days. Hematologic parameters including liver function test were measured at regular intervals, and the duration, composition, administration rate, total calorie of TPN were recorded. The serum levels of total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase were compared between groups after cessation of the study. Results: The autoregressive coefficient of the control group was 0.4419 (p=0.0651) in bilirubin, -0.0431 (p=0.7923) in AST, 0.2398 (p=0.2416) in ALT, and 0.2459 (p=0.1922) in alkaline phosphatase by mixed procedure model when the parameters were referred to the case group. Conclusion: The serum level of total bilirubin did not increase in comparison with that of the control group, but statistically insignificant, when both TPN and UDCA were administered simultaneously from the beginning.