Evaluation of treatment on streptozotocin induced mice diabetes by ppe/rats mesenchymal stem cells

• Main Authors: Chin-Tsu Ma, 馬金足
• Other Authors: Shyh-Ming Kuo
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/q6h5f9

博士 === 義守大學 === 電機工程學系 === 105 === In this present study, we have utilized two different approaches tried to alleviate diabetes mellitus (DM) related stress or advanced to treat the DM. The effect of pepino polyphenolic extract (PPE) on diabetic neuropathy was examined first. PPE was demonstrated to contain coumaroyl and caffeoyl derivatives among polyphenols. The results demonstrated that PPE significantly improved glycaemic control in diabetic mice. These PPE treatments reserved the glutathione (GSH) level, and decreased the thiobarbituric acid reactive substances (TBARS) level, reactive oxygen species (ROS), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, fructose, and glycation intermediates and precursors of advanced glycation end products (AGEs), such as methylglyoxal (MG) and N-(carboxymethyl)lysine (CML), in the sciatic nerves of diabetic mice. PPE also had the effects in improving the nerves of diabetic mice, showing disorganization of the fascicle with numerous small myelinated fibers. The PPE can retain the protein and mRNA levels of glutathione peroxidase (GPX), and decrease the expressions of aldose reductase (AR) and the receptor for the advanced glycation end product (RAGE) in sciatic nerves. These findings support that pepino polyphenolic extract could attenuate oxidative, inflammatory and glycative stress in diabetic peripheral nerves. Advances in mesenchymal stem cells (MSCs) and cell therapies have been promising approaches to treat (DM) since their potent capacities for differentiation into various functional cells match the demands of tissue repair and regeneration. The aim of this study is secondly to examine the effects of nano-sized type I collagen molecules in combination with nicotinamide (NCT) and exendin-4 (EX4) on MSCs differentiation into insulin-secreting cells in vitro and to evaluate their reparative effects against type 2 diabetes mellitus (T2DM) rat in vivo. The obtained results revealed that MSCs showed increased differentiation into insulin-secreting cells with higher mRNA expression for Nkx6.1 and early PDX-1 in the presence of NCT and nano-sized type I collagen molecules. Addition of nano-sized type I collagen fibrils increased morphologically islet-like clusters in differentiated cells. T2DM rats reverted to their normal HbA1 values and exhibited structurally repaired islets in the pancreas implanted with NCT/nano-sized collagen I molecule/EX4-incubated differentiated cells. In short, the combined recipe showed reparative actions on the destructive islet of Langerhans in the pancreas coupled with glucoregulatory effects in T2DM rats in vivo.