PPAR-γ Effects on Retinal Binding Protein 4 (RBP4) and clinical manifestations in Type 2 Diabetes

• Main Authors: Kun-Der Lin, 林昆德
• Other Authors: Shyi-Jang Shin
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/4d3f92

博士 === 高雄醫學大學 === 醫學研究所 === 102 === Diabetes Mellitus (DM) is a major issue of public health around the world. The pathophysiological factors of type 2 DM are diverse, including the genetic and environmental factors. The insulin resistance, abdominal obesity, and sick of adipose tissue have major effects on metabolic syndrome and they play an important role in contributing to type 2 DM. We focus on serum retinol-binding protein 4 (RBP4) secreted mainly by adipocytes, and study its effect on insulin resistance clinically. We analyze the differences of RBP4 in patients with or without type 2 DM, and the interactions with other clinical factors. The RBP4 also regulates STRA6/CRBP-I/JAK2/STAT5 pathway and causes cell apoptosis in vitro. PPAR-γ agonists can improve insulin resistance, affect the differentiations of adipocytes, and reduce the inflammations of endothelial cells and slow the progression of diabetic nephropathy. We study the effects of PPAR-γ on serum RBP4 and adiponectin in our type 2 diabetic patients. Thiazolidinedione(TZD) is a PPAR-γ agonist, and is widely used to treat type 2 DM in recent years for controlling the blood glucose through enhancing insulin sensitivity. Pioglitazone® is one of the TZDs and its common side effects are body weight gain, congestive heart failure, lower legs edema and etc. In 2011, FDA warned the higher risk of developing bladder cancer in men and atypical bone fracture in women after long term treatments of pioglitazone® in patients with type 2 DM by meta-analysis announced in mid-2011. Some of our patients withdrew pioglitazone® treatment since that time. So, we designed a prospective study to observe the long-term effects in our type 2 DM patients treated with pioglitazone® and who withdrew pioglitazone® treatment. Our results showed that the increase of RBP4 correlates with the increase of insulin resistance in our diabetic patients; and the serum RBP4 is decreased after treatment of pioglitazone 30mg/day for 3 months. The serum RBP4 is correlated to the stages of diabetic nephropathy and also correlated with renal function and uric acid level in our clinical findings. The side effects of pioglitazone® treatment including body weight gain, decreases of RBC, hemoglobin (Hb), and hematocrit (Hct) in type 2 diabetic patients. After stopping pioglitazone® treatment for 10 months, the body weight gain reversed but surprisingly, RBC, Hb and Hct did not. It implies that pioglitazone causes bone marrow suppression and this effect persisted more than 10 months. This finding provokes us to seriously consider the persistent effects of PPAR-γ agonist on the hematopoietic system in type 2 diabetic patients. In these series study, we study the PPAR-γ effects in our type 2 DM, and focus on adipocytokine, RBP4. The serum RBP4 is correlated with diabetic nephropathy stage, renal function and serum uric acid level. Pioglitazone, a PPAR-γ agonist, can decrease RBP4 level in type 2 DM and increase insulin sensitivity. Long term PPAR-γ treatment also causes tiny but significantly reduction of hematopoietic system and reduces RBC, Hb and Hct level in type 2 DM. These findings can provide the additional information to treat our type 2 diabetic patients in clinical practice.