Diabetes & Metabolism Journal

Original Articles

ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity: Yeul Bum Park, Yun Jung Choi, So Young Park, Jong Yeon Kim, Seong Ho Kim, Dae Kyu Song, Kyu Chang Won, Yong Woon Kim; Diabetes Metab J. 2011;35(3):219-225. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.219

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Background

The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (K_ATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight.

Methods

To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the K_ATP channel.

Results

The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice.

Conclusion

These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.

Citations

Citations to this article as recorded by

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Taurine-Mediated Restoration of Glucose Sensitivity of Pancreatic Beta Cells in OLETF Rats.: So Yeon Kim, Keun Gyu Park, In Kyu Lee, Seong Il Nam, Dae Kyu Song; Korean Diabetes J. 2005;29(3):198-205. Published online May 1, 2005

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Abstract PDF: BACKGROUND
An OLETF(Otsuka Long-Evans Tokushima Fatty) rat is a model of type 2 diabetes that is characterized by obesity-induced insulin resistance. Taurine has been known to be beneficial for type 2 diabetes. This study evaluated the potential taurine effect on the insulin response to high glucose in the islets of OLETF rats. METHODS: One percent of taurine was put in the drinking water for the taurine group of OLETF rats at the time of their being 20 to 39 weeks of age. At 40 weeks, the pancreatic islets and beta cells were obtained to measure the glucose-stimulated insulin secretion(GSIS) and the ATP-sensitive K+(KATP) channel current. RESULTS: Taurine supplementation had no effect on the weight change of the rats when this was measured weekly from 20 to 39 weeks(mean+/-SE: 702+/-19g in the control group vs. 688+/-18g in the taurine group at the 39th week). However, the GSIS was significantly potentiated in the taurine-treated rats(8.9+/-1.3% vs. 13.2+/-3.2% of the total secreted at 15 mM glucose for 1h). The glucose-induced KATP channel inhibition in the beta cells was also greater in the taurine group. CONCLUSION: Taurine supplementation is a beneficial tool for the restoration of GSIS in the pancreatic islet of the OLETF rats. Maintenance of blood taurine level may be important in treating type 2 diabetic patients, who are subject to a low blood level of taurine

A Differential Effect of Intracellular ATP on Skeletal-and Smooth Muscle-Type KATP Channel Activities.: Oh Dae Kwon, Jeong Geun Lim, Haeng Gyun Kim, Dae Kwang Kim, Jae Seok Hwang, Keun Gyu Park, Sung Hee Park, Chi Heum Cho, In Kyu Lee, Dae Kyu Song; Korean Diabetes J. 2003;27(4):332-342. Published online August 1, 2003

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Abstract PDF: BACKGROUND
The ATP-sensitive potassium (KATP) channel comprises an inwardly- rectifying K+ channel (Kir) and a sulfonylurea receptor(SUR). This study investigated the mechanism of different ATP sensitivity between skeletal-(Kir6.2/SUR2A) and smooth muscle- (Kir6.2/SUR2B) type KATP channels. METHODS: Messenger RNAs encoding mouse Kir6.2, and rat SUR2A or 2B were co-injected into Xenopus Laevis oocytes to express each type of KATP channel. Using the inside-out patch clamp technique, the channel currents for MgATP sensitivity were measured and analyzed. RESULTS: By addition of 100 microM of MgATP, the current initially decreased and then slowly increased in Kir6.2/SUR2A. This gradual, ATP sensitivity decrease during prolonged MgATP application was totally blocked by LY 294002, a pho- sphatidylinositol-3 and -4 kinase inhibitor. In contrast, a rather rapid sensitivity decrease after initial inhibition was observed in Kir6.2/SUR2B by 100 microM of ATP, which was not blocked by LY 294002. This channel activation was Mg2+- dependent, suggesting that ATP hydrolysis is critical. CONCLUSION: This result supports the idea that the ability of MgATP to stimulate Kir6.2/SUR2B channels reflects a faster rate of ATP hydrolysis at NBD2 of SUR2B.

Alterations of Plasma Atrial Natriuretic Peptide and its mRNA in Non-insulin Dependent Diabetic Model of Rats.: Byeong Dae Yoo, Won Kyun Park, Young Su Hong, Dae Kyu Song, Jae Hoon Bae; Korean Diabetes J. 2000;24(4):421-430. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus has led to change in fluid and electrolyte balance and consequently affected blood volume and blood pressure. These changes can trigger the secretion and synthesis of atrial natriuretic peptide (ANP) from both atrial and extra-atrial tissues. ANP plays an important role in the regulations of body fluid balance and blood pressure. Therefore, this study was carried out to elucidate whether or not atrial and extra-atrial synthesis of ANP is influenced in experimental non-insulin dependent diabetes mellitus (NIDDM) rats. METHODS: Neonatal rats were induced into NIDDM rats by single injection of streptozotocin (80 mg/kg). Plasma ANP level was measured by the use of radioimmunoassay method and the ANP mRNA expressions from the right atrium, left ventricle, hypothalamus and kidney were analyzed by reverse transcription- polymerase chain reaction with [32P]-dCTP at 8 weeks after injection of streptozotocin or citrate buffer. RESULTS: Blood glucose was more significantly increased at 2 hours after glucose loading in NIDDM rats than control rats. Plasma concentration of ANP tended to significantly increase in NIDDM rats compared with control rats. The expressions of ANP mRNA from each tissue were observed in different patterns. Right atrial ANP mRNA expression revealed non-significant increasing trend in NIDDM rats, whereas left ventricular ANP mRNA did not have difference. However, both hypothalamic and renal ANP mRNA expressions in NIDDM rats were significantly increased. CONCLUSION: These results indicate that the enhanced expressions of hypothalamic and renal ANP mRNA act as an important regulator of electrolytes and body fluid volume in neonatally streptozotocin-induced NIDDM rats.

Differential Effects of Palmitate and Docosahexaenoic acid on ATP-sensitive K+ Channel Activity of Pancreatic beta-cells.: Yong Woon Kim, Kyeung Oh Doh, Dae Kyu Song, Jae Hoon Bae, Won Kyun Park, Kyu Jang Won, Hyoung Woo Lee, Suck Kang Lee; Korean Diabetes J. 1999;23(6):768-776. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Elevated levels of free fatty acids markedly enhance insulin secretion. However, dietary polyunsaturated fatty supplementation decrease insulin secretion. The effects of different type of fatty acids on cultured pancreatic beta cell remain controversy. Therefore, the specific goal of this study was to confirm the effect of palmitate and docosahexaenoic acid (DHA) on pancreatic beta-cells. We measured ATP-sensitive K+ (KATP) channel activity by patch clamp technique. METHOD: Pancreatic beta-cells were isolated from male Sprague-Dawley rats and cultured on the cover glass in the culture media. KATP channel activity of pancreatic beta-cells were measured by the cell-attached mode of the patch clamp technique. We treated 30 micrometer of palmitate and DHA dissolved with 3% albumin solution. RESULT: 30 micrometer of palmitate inhibited KATP channel activity. Moreover, after additions of 5 and 10 mM glucose, additional and dose dependent inhibitory effects were revealed. However, 30 micrometer of DHA did not have these additional inhibitory effect treated with 5 and lOmM glucose. CONCLUSION: Palmitate as a saturated fatty acid inhibited activity of KATP channel and increased inhibitory effect of glucose on this channel activity, however, DHA as a polyunsaturated fatty acid attenuated inhibitory effect of glucose on this channel activity.

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