Diabetes & Metabolism Journal

Volume 26(3); June 2002

Reviews

Adiponectin and Resistin.: Kyung Mook Choi, Sei Hyun Baik; Korean Diabetes J. 2002;26(3):147-152. Published online June 1, 2002

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Abstract PDF: No abstract available.

Type 1 diabetes: autoimmune pathogenesis and its heterogeneity.: Choon Hee Chung; Korean Diabetes J. 2002;26(3):153-163. Published online June 1, 2002

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Abstract PDF: No abstract available.

Editorial

Secretion and Action of Ghrelin.: Tae Wha Kim, Dong Sun Kim; Korean Diabetes J. 2002;26(3):164-168. Published online June 1, 2002

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Original Articles

Expression of ghrelin and its receptor according to feeding state in rats.: Min Seon Kim, Cho Ya Yoon, Young Joo Park, Hyung Kyu Park, Chen Ji Jin, Kyong Han Park, Chan Soo Shin, Kyong Soo Park, Seong Youn Kim, Bo Youn Cho, Hong Kyu Lee; Korean Diabetes J. 2002;26(3):169-178. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Ghrelin is a newly discovered gut peptide, produced mainly in the stomach, which is secreted into the circulating blood and acts on the hypothalamus and the pituitary gland. Although ghrelin was originally identified as an endogenous growth hormone secretagogue, recent studies have suggested its role is in the regulation of food intake and energy homeostasis. The aim of this study was to investigate changes in the expression of ghrelin in the stomach, and of its receptors in the hypothalamus and the pituitary gland in relation to the feeding state. METHODS: Sprague Dawley male rats, divided into 3 groups, freely fed, fasted for 48 hrs and fasted for 48 hrs followed by feeding for 24 hrs, were investigated. The stomach fundus, the hypothalamus and the pituitary glands were collected. The gastric ghrelin mRNA expression was determined by Northern blot analysis and the ghrelin protein by immunohistochemistry. The ghrelin receptor mRNA levels in the hypothalamus and anterior pituitary gland were determined by real time PCR. RESULTS: The ghrelin mRNA levels in the stomach were increased by fasting but reduced again by allowing feeding. The number of ghrelin-immunoreactive gastric epithelial cells tended to increase with fasting. Moreover, the ghrelin receptor mRNA levels increased fold in the hypothalamus, and about 3 fold in the anterior pituitary gland harvested from the rats that had fasted for 48 hrs compared to those that were freely fed. CONCLUSION: Our data demonstrate that expression of both ghrelin in stomach and its receptor in target organs increased in the fasted state, which would be helpful for magnifying the orexigenic effect of ghrelin in the negative energy balance state. Dynamic changes in ghrelin and ghrelin receptor according to altered metabolic state may suggest a physiologic role of ghrelin in the regulation of energy homeostasis.

Effects of Antioxidants on Ethidium Bromide-induced Inhibition of Insulin Secretion in Rat Pancreatic Islets.: Chul Hee Kim, Chan Hee Kim, Hyeong Kyu Park, Kyo Il Suh, Ki Up Lee; Korean Diabetes J. 2002;26(3):179-187. Published online June 1, 2002

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Abstract PDF: BACKGROUND
It was recently shown that mitochondrial function in pancreatic beta-cells is essential in nutrient-stimulated insulin secretion. The inhibition of mitochondrial DNA (mtDNA) transcription by ethidium bromide (EtBr) has been reported to suppress glucose-induced insulin secretion in beta-cell lines. This study was undertaken to examine the effects of EtBr on insulin secretion in isolated normal rat pancreatic islets, and to see whether antioxidants could protect the beta-cell function against the EtBr-induced impairment. METHODS: Pancreatic islets of normal Sprague-Dawley rats were isolated by intraductal injection of collagenase followed by Ficoll-gradient centrifugation. Isolated islets were treated with 0.2 +/- 2.0 microgram/mL of EtBr for 2 to 6 days, and the glucose-stimulated insulin secretion measured. The effects of the antioxidant, vitamin E and alpha-lipoic acid, on the EtBr-induced inhibition of insulin secretion were also examined. RESULTS: EtBr inhibited the basal and glucose-stimulated insulin secretion in normal rat pancreatic islets in a dose- and time-dependent manner. Vitamin E and alpha-lipoic acid prevented the EtBr-induced inhibition of insulin secretion. CONCLUSION: Our results show that antioxidant can protect normal rat pancreatic islets from the EtBr-induced inhibition of insulin secretion. This suggests that oxidative stress is involved in the pathogenesis of the insulin secretory defect associated with mitochondrial dysfunction.

Insulin Resistance and severity of coronary artery diseases in Patients with Coronary Artery Diseases.: Dae Jung Kim, Jae Hyun Nam, Dong Hoon Choi, Hyeung Jin Kim, Soo Kyung Kim, Se Hwa Kim, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2002;26(3):189-198. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Insulin resistance (IR) has been identified as a risk factor of atherosclerosis, which may be induced through a mechanism brought about by hypertension, obesity, glucose intolerance and dyslipidemia. The purpose of this study was to investigate the relationship between coronary artery disease (CAD) and insulin resistance. METHODS: Of 92 subjects having undergone coronary angiography 70 with significantly stenotic coronary artery were designated as the CAD group, with the other 22, without stenosis, as the control group. The CAD group was subdivided into 3 smaller groups according to the severity of their CAD; these being 1-vessel disease (group 1, n=31), 2-vessel disease (group 2, n=25), and 3-vessel disease (group 3, n=14). RESULTS: Kitt for patients with CAD was significantly lower than in the control group, and also for those in group 1 compared to groups 2 and 3, 2.72+/-1.29, 2.25+/-0.68 and 2.21+/-0.78%/min, with that of the controls being 3.01+/-1.22%/min p<0.05). There were significant differences between the IR group and the non-IR group in the common carotid artery intima-media thickness (1.09mm vs. 0.87mm, p<0.05), the waist-hip ratio (1.09 vs. 0.93, p<0.05) and the body fat contents (32% vs. 27%, p<0.05).Insulin resistance was assessed by the short insulin tolerance test, and the insulin resistance (IR) group was defined as having a Kitt less than 2.5%/min. CONCLUSION: These results suggest that insulin resistance is an important risk factor for CAD, and is related to the severity of coronary atherosclerosis.

Evaluation of Erectile Dysfunction in type 2 Diabetes: Prevalence, Clinical characteristics and Treatment effect of sildenafil citrate.: Byoung Hyun Park, Joung Sik Rim, Chung Gu Cho; Korean Diabetes J. 2002;26(3):199-207. Published online June 1, 2002

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Abstract PDF: BACKGROUND
The prevalence of erectile dysfunction has been reported to be three times higher in diabetics than nondiabetics. As the majority of type 2 diabetes develops later in life, any associated erectile dysfunction often ignored by physician as well as patients. The purpose of this study was to investigated the prevalence of erectile dysfunction in type 2 diabetes and to find any related clinical characteristics and the effect of sildenafil citrate treatment in these types of patient. METHODS: We studied 75 male type 2 diabetics who visited the Wonkwang University Hospital between March and July, 2000, and analyzed their International Index of Erectile Function questionaires. Erectile dysfunction was defined as a the total score less than 24 points according to the answers to six questions about erections. According to this definition, our patients were divided into two groups; the presence, and the absence, of erectile dysfunction. We also obtained details from the patients relating to their history of smoking, alcohol, consumption, diabetic foots and hypertension; measured their current weight, height, HbA1c, lipoprotein (a), lipid profile, albumin and QTc and evaluated the presence of diabetic retinopathy, nephropathy and neuropathy. A single oral dose of sildenafil, 25 mg, was started and the effect assessed by a global efficacy question every 4 weeks for 12 weeks. If there was no effect, we increased the dose to 50 or 100 mg. RESULTS: 1) The prevalence of erectile dysfunction in type 2 diabetics in this study was 77.3%. Most patients (86.2%) wanted their erectile dysfunction treated, but a minority (31%) had visited a private clinic to discuss the problem. 2) The prevalence of erectile dysfunction increased with age, increased duration of diabetes and HbA1c. The Body Mass Index (BMI) and serum albumin were inversely related to erectile dysfunction. 3) The erectile dysfunction was significantly associated with diabetic autonomic neuropathy and retinopathy. 4) The score from the questionaires of five relevant domains of sexual function (these being, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) were lower in the erectile dysfunctional group. 5) 18 patients were prescribed sildenafil, 61.6% of which reported improved erections by the end of the study, with 50% of these being satisfied with their erections. There were no side effects causing discontinuation of treatment. CONCLUSION: The prevalence of erectile dysfunction in type 2 diabetics in this study was 77.3%. The prevalence of erectile dysfunction increased with age, increased duration of diabetes and HbA1c. The BMI and serum albumin were inversely related to erectile dysfunction. The effect of sildenafil was simillar to that reported previously for other countries, and was effective in the treatment of erectile dysfunction in type 2 diabetics.

Detection of Diabetic Autonomic Neuropathy by 24-Hour Heart Rate Variability Analysis in Type 2 Diabetes Mellitus Patients.: Young Hee Rho, Nan Hee Kim, Dong Lim Kim, Dong Hyun Shin, Sin Gon Kim, Kyung Mook Choi, Woo Hyuk Song, Sei Hyun Baik, Woo Keun Seo, Min Kyu Park, Dong Seop Choi; Korean Diabetes J. 2002;26(3):208-219. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Diabetic autonomic neuropathy is a relatively common diabetic complication, associated with high long-term mortality. Ewing's test is known as the 'gold standard' for evaluating and diagnosing this disease, yet is not widely used due to the inconvenient procedures of the test. 24-hour Holter EKG monitoring, and the analytical product, heart rate variability, is being introduced as a relatively simple and reliable procedure for the evaluation of diabetic autonomic neuropathy. We explored whether such heart rate variability products derived from Holter monitoring, correlated with the presence, absence, or severity of diabetes mellitus, and whether it correlated well with conventional autonomic tests. METHODS: We compared 59 type 2 diabetic patients with 71 normal subjects. All underwent 24-hr Holter EKG monitoring and basic autonomic evaluations, such as the head-up tilting, hand grip, and deep breathing-heart rate variability tests. Those who had diabetes also underwent evaluation for basic blood chemistry, and complication studies, for things such as: 24-hour urine albumin excretion, fundoscopy and nerve conduction. RESULTS: Variables for heart rate variability were expressed as SDDN, rMSSD, LF, HF, and LF/HF, where SDDN is the Standard Deviation of all RR intervals, rMSSD the square root of the mean of the sum of the squares of differences between adjacent RR intervals, LF the power in the Low Frequency range and HF the power in the High Frequency range, with LF/HF being the ratio between LF and HF. Heart rate variability was significantly lower in terms of rMSSD, LF, HF, but not in terms of the LF/HF ratio, for the diabetic patients compared to the normal subjects. These three variables also correlated with the conventional autonomic tests of systolic blood pressure changes during standing up (negatively), and heart rate variability during deep breathing (positively). SDDN, rMSSD, LF, and HF also correlated negatively with the duration of diabetes. SDDN, LF and HF were significantly lower among patients who had complications such as: retinopathy, nephropathy or peripheral neuropathy, than in those who did not. CONCLUSION: Heart rate variability was lower in type 2 diabetic patients than the control subjects, which correlated well with the duration of diabetes mellitus, diabetic chronic complications and the conventional autonomic nervous function tests, so could be an useful adjunct or even a replacement, for conventional autonomic nervous system testing procedures. More research is needed in this field.

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