당뇨 유발 동물 모델에서 Leptin, Adiponectin, Adiponectin 수용체 mRNA 발현에 대한 항우울제의 영향
The Effects of Antidepressants on the Leptin, Adiponectin, and Adiponectin Receptor mRNA Expression in Model Diabetogenic Rats
1
조회
0
다운로드
0
인용
0
참고문헌
초록
Objectives: Weight gain and glucose intolerance are the most common symptoms of metabolic syndrome. Certain patients complain of weight-change and hyperglycemia after receiving antidepressants. Our study evaluated the effects of antidepressants on serum glucose and energy metabolism. Methods: Subjects were 32 Otsuka Long-Evans Tokushima Fatty (OLETF) and 35 wild-type Long-Evans Tokushima Otsuka (LETO) rats. From age 11 weeks, the rats were divided into 4subgroups within each strain. We administered the designated antidepressant-amitriptyline,fluoxetine, or mirtazapine-to these subgroups, allocating the fourth as the control. After exactly 4 weeks’ medication, we sacrificed the animals and checked their weight, glucose, insulin,leptin, adiponectin, and expression of adiponectin receptor mRNA. Results: Fluoxetine subgroups in both strains gained the least weight. The glucose, triglyceride,and cholesterol levels of all OLETF antidepressant subgroups did not differ from the controls. Adiponectins in amitriptyline- and mirtazapine-subgroups were higher than control. All antidepressant subgroups showed elevated expressions of adiponectin receptor mRNA in fat,muscle, and the pancreas. Conclusion: Amitriptyline and mirtazapine seem to regulate adiponectin and expression of adiponectin receptor mRNA. Even though the underlying mechanisms were different, we conclude none of the antidepressants would have negative influences on energy metabolism in diabetogenic animals.
Abstract
Objectives: Weight gain and glucose intolerance are the most common symptoms of metabolic syndrome. Certain patients complain of weight-change and hyperglycemia after receiving antidepressants. Our study evaluated the effects of antidepressants on serum glucose and energy metabolism. Methods: Subjects were 32 Otsuka Long-Evans Tokushima Fatty (OLETF) and 35 wild-type Long-Evans Tokushima Otsuka (LETO) rats. From age 11 weeks, the rats were divided into 4subgroups within each strain. We administered the designated antidepressant-amitriptyline,fluoxetine, or mirtazapine-to these subgroups, allocating the fourth as the control. After exactly 4 weeks’ medication, we sacrificed the animals and checked their weight, glucose, insulin,leptin, adiponectin, and expression of adiponectin receptor mRNA. Results: Fluoxetine subgroups in both strains gained the least weight. The glucose, triglyceride,and cholesterol levels of all OLETF antidepressant subgroups did not differ from the controls. Adiponectins in amitriptyline- and mirtazapine-subgroups were higher than control. All antidepressant subgroups showed elevated expressions of adiponectin receptor mRNA in fat,muscle, and the pancreas. Conclusion: Amitriptyline and mirtazapine seem to regulate adiponectin and expression of adiponectin receptor mRNA. Even though the underlying mechanisms were different, we conclude none of the antidepressants would have negative influences on energy metabolism in diabetogenic animals.
참고문헌 (31)
- Foster DW, "Diabetes Mellitus in Harrison’s Principles of Internal medicine", pp.2060~2070 (1998), McGraw-Hill
- Sussman N, "Review of atypical antipsychotics and weight gain", J Clin Psychiatry, 62(Suppl 23), pp.5~12 (2001)
- McIntyre RS, "Mechanisms of antipsychotic-induced weight gain", J Clin Psychiatry, 62(Suppl 23), pp.23~29 (2001)
- Fernstrom MH, "Antidepressant-induced weight gain: a comparison study of four medications", Psychiatry Res, 26, pp.265~271 (1988)
- Erenmemisoglu A, "Effect of some antidepressants on glycaemia and insulin levels of normoglycaemic and alloxan-induced hyperglycaemic mice", J Pharm Pharmacol, 51, pp.741~743 (1999)
- Sugimoto Y, "The tricyclic antidepressant clomipramine increases plasma glucose levels of mice", J Pharmacol Sci, 93, pp.74~79 (2003)
- Breum L, "Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity", Metabolism, 44, pp.1570~1576 (1995)
- Maheux P, "Fluoxetine improves insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus independently of weight loss", Int J Obes Relat Metab Disord, 21, pp.97~102 (1997)
- Chen JL, "Hypertriglyceridemia, acute pancreatitis, and diabetic ketoacidosis possibly associated with mirtazapine therapy: a case report", Pharmacotherapy, 23, pp.940~944 (2003)
- Fisfalen ME, "Glucose dysregulation and mirtazapine-induced weight gain", Am J Psychiatry, 160, pp.797~ (2003)
- Mihara IQ, "The impact of mirtazapine compared with non-TCA antidepressants on weight change in nursing facility residents", Consult Pharm, 20, pp.217~223 (2005)
- Kim SW, "Pathophysiology of Obesity and Metabolic Syndrome", 대한비만학회지, 11, pp.213~225 (2002)
- Stefan N, "Adiponectin--its role in metabolism and beyond", Horm Metab Res, 34, pp.469~474 (2002)
- Meier U, "Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin", Clin Chem, 50, pp.1511~1525 (2004)
- Trayhurn P, "Appetite and energy balance signals from adipocytes", Philos Trans R Soc Lond B Biol Sci, 361, pp.1237~1249 (2006)
- Becker DJ, "Diet- and diabetes-induced changes of ob gene expression in rat adipose tissue", FEBS Lett, 371, pp.324~328 (1995)
- Arita Y, "Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity", Biochem Biophys Res Commun, 257, pp.79~83 (1999)
- 최경묵, "혈청 아디포넥틴 농도와 대사증후군 발병의 연관성", 대한내분비학회지, 19(5), pp.482~500 (2004), 대한내분비학회
- 김미진, "제2형 당뇨병 환자에서 혈중 Adiponectin과 인슐린 저항성과의 관계", Diabetes and Metabolism Journal, 27(3), pp.260~271 (2003), 대한당뇨병학회
- Bouskila M, "Adiponectin: a relevant player in PPARgamma-agonist-mediated improvements in hepatic insulin sensitivity?", Int J Obes (Lond), 29(Suppl 1), pp.S17~S23 (2005)
- Kadowaki T, "Adiponectin and adiponectin receptors", Endocr Rev, 26, pp.439~451 (2005)
- Whitehead JP, "Adiponectin--a key adipokine in the metabolic syndrome", Diabetes Obes Metab, 8, pp.264~280 (2006)
- Kawano K, "OLETF (Otsuka Long-Evans Tokushima Fatty) rat: a new NIDDM rat strain", Diabetes Res Clin Pract, 24(Suppl), pp.S317~S320 (1994)
- Funakoshi A, "Disrupted cholecyctokinin type-A receptor gene in OLETF rats in Obesity and NIDDM, Lessons from the OLETF Rat", pp.87~98 (1999), Elsevier
- Yoshihide T, "Antiobese and antidiabetic effects of ß3-adrenergic receptor agonist in OLETF rats in Obesity and NIDDM, Lessons from the OLETF Rat", pp.79~85 (1999), Elsevier
- Sato T, "Molecular mechanisms of insulin resistance in skeletal muscle of the OLETF rat in Obesity and NIDDM, Lessons from the OLETF rat", pp.67~77 (1999), Elsevier Science B.V
- Dryden S, "Decreased plasma leptin levels in lean and obese Zucker rats after treatment with the serotonin reuptake inhibitor fluoxetine", Horm Metab Res, 31, pp.363~366 (1999)
- Gutierrez A, "Effects of fluoxetine administration on neuropeptide y and orexins in obese zucker rat hypothalamus", Obes Res, 10, pp.532~540 (2002)
- Cypess AM, "Identification and importance of brown adipose tissue in adult humans", N Engl J Med, 360, pp.1509~1517 (2009)
- Ravussin E, "Have we entered the brown adipose tissue renaissance?", Obes Rev, 10, pp.265~268 (2009)
- Heiser P, "Effects of different antipsychotics and the antidepressant mirtazapine on glucose transporter mRNA levels in human blood cells", J Psychiatr Res, 40, pp.374~379 (2006)