Tae Kyoon Kim

Comparison of pancreatic beta cells and alpha cells under hyperglycemia: Inverse coupling in pAkt-FoxO1

Type 2 diabetes manifests beta cell deficiencies and alpha cell expansion which is consistent with relative insulin deficiency and glucagon oversecretion. The effects of hyperglycemia on alpha cells are not as understood in comparison to beta cells. Hyperglycemia increases oxidative stress, which induces Akt activation or FoxO activation, depending on cell type. Several studies independently reported that FoxO1 translocations in alpha cells and beta cells were opposite. We compared the responses of pancreatic alpha cells and beta cells against hyperglycemia. Alpha TC-1 cells and Beta TC-6 cells were incubated with control (5mM Glucose) or high glucose (33mM Glucose) with or without PI3K inhibitor or FoxO1 inhibitor. We assessed PI3K, pAkt and phosphorylated FoxO1 (pFoxO1) in both cell lines. Immunostaining of BrdU and FoxO1 was detected by green fluorescence microscopy and confocal microscopy. Hyperglycemia and H2O2 decreased PI3K and pAKT in beta cells, but increased them in alpha cells. FoxO1 localizations and pFoxO1 expressions between alpha cells and beta cells were opposite. Proliferation of beta cells was decreased, but alpha cell proliferation was increased under hyperglycemia. Antioxidant enzymes including superoxide dismutase (SOD) and catalase were increased in beta cells and they were reversed with FoxO1 inhibitor treatment. Increased proliferation in alpha cells under hyperglycemia was attenuated with PI3K inhibitor. In conclusion, hyperglycemia increased alpha cell proliferation and glucagon contents which are opposite to beta cells. These differences may be related to contrasting PI3K/pAkt changes in both cells and subsequent FoxO1 modulation.

The value of the mean peak systolic velocity of the superior thyroidal artery in the differential diagnosis of thyrotoxicosis

Purpose: The aim of this study was to validate the superior thyroidal artery mean peak systolic velocity (STA-mPSV) as an alternative to other diagnostic parameters in the differentiation of the causes of thyrotoxicosis in Korean patients. Methods: This study was conducted with newly diagnosed and untreated thyrotoxic patients. Forty patients were diagnosed with Graves disease (GD) and 20 patients with destructive thyroiditis (DT). Another 60 healthy subjects without thyroid disease participated as the control group. Blood samples were taken to evaluate the thyroid function and thyroid autoantibodies (TRAb). Twenty-four hour radioactive iodine uptake (RAIU) scanning was performed to confirm GD or DT. The STA-mPSV was measured using color Doppler ultrasonography. Results: The STA-mPSV was significantly higher in the untreated GD group than in the DT group (GD, 78.96±29.04 cm/sec; DT, 29.97±14.67 cm/sec; control, 17.55±4.99 cm/sec; P<0.001). The area under the curve (AUC) of the STA-mPSV for the differential diagnosis of untreated GD and DT was 0.9506 (optimal cutoff value, 41.3 cm/sec; sensitivity, 95%, 38/40; specificity, 85%, 17/20) in the receiver operating characteristic analysis. The AUC values of the STA-mPSV, RAIU, and TRAb were 0.9506, 1, and 0.9988, respectively (P=0.159). Conclusion: In clinical practice, the STA-mPSV has a diagnostic value similar to that of the TRAb and 24-hour RAIU in the differential diagnosis of newly diagnosed Korean thyrotoxic patients.

Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress

ABSTRACT Background: Ginsenoside Rg3 has been proposed to mediate anti-diabetic effects, but their direct effect on pancreatic β cell viability and mechanisms are not clearly understood. Recent studies suggest that intermittent high glucose (IHG) could be more harmful to pancreatic β cells than sustained high glucose. There are few reports about the effect of the ginsenosideRg3 to β cell apoptosis and proliferation against IHG. Methods: INS-1 cells were treated with alternative glucose concentration with or without ginsenoside Rg3. Cell apoptosis and viability were detected by Annexin V staining and MTT assay. The activation of mitogen-activated protein kinases (MAPKs) was analyzed by Western blotting using specific antibodies. Quantification of secreted insulin protein was measured using rat/mouse Insulin ELISA kits. Bromodeoxyuridine (BrdU) staining and florescence in situ hybridization (FISH) analysis was performed to compare cell proliferation. Result: INS-1 cell viability was decreased under IHG and increased with Rg3 treatment.Rg3 significantly reduced the apoptotic INS-1 cells against IHG. The quantification of secreted insulin concentration was increased with Rg3. Rg3 increased INS-1 cell proliferation. ERK and p38 MAPK pathways reduced by IHG were activated by the ginsenoside Rg3. Conclusion: Ginsenoside Rg3 protected INS-1 cell death from IHG with reducing apoptosis and increasing proliferation.

Diabetic Myonecrosis in a Patient with Hepatitis B-Induced Liver Cirrhosis

Diabetic myonecrosis-a rare complication of long-standing, poorly controlled diabetes mellitus-typically presents with acute-onset muscle pain, is self-limiting, and responds well to conservative management. We report a case of diabetic myonecrosis in a 33-year-old man with hepatitis B-induced liver cirrhosis and type 2 diabetes who presented with abdominal distension and pain in the left thigh. Diabetic myonecrosis was diagnosed based on clinical presentation, radiological findings, magnetic resonance imaging and histopathological investigations; he was successfully treated conservatively with insulin and analgesics. Diabetic myonecrosis should be considered in the differential diagnosis of muscle pain in patients with diabetes.

Co-Culture of α TC-6 Cells and β TC-1 Cells: Morphology and Function.

Background In vitro experiments using only β-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially α- and β-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with α- and β-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets. Methods α TC-6 cells and β TC-1 cells were maintained in Dulbeccos Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5×105) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS). Results α TC-6 and β TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. β TC-1 cells showed both β-β and β-α cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than β TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for β-cells alone (P=0.04). Compared to islets, the α-/β-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09). Conclusion α TC-6 and β TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.

False Positive Radioiodinated Metaiodobenzylguanidine (123I-MIBG) Uptake in Undifferentiated Adrenal Malignant Tumor

123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy is a widely used functional imaging tool with a high degree of sensitivity and specificity in diagnosis of pheochromocytoma. However, rare cases of false positive reactions have been reported. A 67-year-old male patient was admitted with epigastric pain. Abdominal computed tomography (CT) revealed a heterogeneous left adrenal mass 6 cm in diameter; following hormone testing, 123I-MIBG scintigraphy was performed to determine the presence of pheochromocytoma, which confirmed eccentric uptake by a large left adrenal gland mass. Chest CT and PET-CT confirmed metastatic lymphadenopathy; therefore, endobronchial ultrasound transbronchial needle aspiration was performed. Metastatic carcinoma of unknown origin was suspected from a lymph node biopsy, and surgical resection was performed for definitive diagnosis and correction of excess hormonal secretion. A final diagnosis of undifferentiated adrenal malignant tumor was rendered, instead of histologically malignant pheochromocytoma, despite the uptake of 123I-MIBG demonstrated by scintigraphy.