| BackgroundDiabetes Millitus(DM) is a group characterized by chronic hyperglycemia, metabolic disease and which is caused by the interaction of genetic and environmental factors. Which is also a carbohydrates、fat and protein metabolism disorder chronic diseases due to the body relative or absolute lack of insulin or target cells decreased insulin sensitivity, or insulin inherent structural defects and its major feature is hyperglycemia, glucosuria. Its clinical performance is polydipsia、 polyphagia、polyuria and weight loss. And it will enable some of the tissue or organ morphological changes and dysfunction occurs, complicated by ketoacidosis, limb gangrene, polyneuritis, blindness and kidney failure et al. Which is one of the major diseases that endangering human health. Diabetes is divided into type1diabetes、type2diabetes、gestational diabetes and other special types of diabetes. In lot of patients with diabetes, which account for nearly85%-90%of patients with type2diabetes. Type2diabetes mellitus (T2DM) is a chronic systemic metabolic disease, which is characterized by insulin resistance and islet function decline. According to the data released by the International Diabetes Federation on World Diabetes Day2011: people suffered from the diabetes has reached to366million in global, up to4.6million people died due to the diabetes annually (an average of one person every7seconds). Which is one of the ten diseases that lead to disability, and reached an alarming＄465billion annually in the cost of the disease. The status quo of China’s diabetes is similarly grim. According to the data of the Asian Diabetes Association, the total number of the diabetes has reached to92.4million in2012, the incidence rate up to9.7%.The etiology and pathogenesis of diabetes still has not been fully elucidated. Diabetes is not a single disease, but a complex aetiology of the syndrome, the result of the interaction of a variety of factors, including genetic and environmental factors. Currently, the treatment of diabetes is a comprehensive medical treatment, including the traditional diet, exercise, oral hypoglycemic drugs and insulin injections. However, the study confirmed that these comprehensive medical treatment can only control the blood glucose in a reasonable range, but can not fundamentally prevent the occurrence and development of complications.As early as in the1950s, the clinical observation found that the blood glucose in these obese patients with type2diabetes who underwent the bariatric surgery can be well controlled, and can even be completely broke away from the drug treatment. Since then, bariatric surgery is becoming more widely used in patients with type2diabetes. These bariatric surgery effectively reduce the patient’s weight, while also effectively improve most of the coexisting glucose metabolism disorders. Continuous research and evidence of these bariatric surgery has a better therapeutic effect on normal-weight patients with diabetes.At present,mainly surgical procedure of weight loss and diabetes mellitus surgery including:Roux-en-Y gastric bypass (RYGBP), Mini Gastric Bypass,(MGB), Biliopancreatic Diversion,(BDP) or Biliopancreatic Diversion with Duodenanl Switch(BPD-DS), Sleeve Gastrectomy(SG) and AdjustableGastric Bypass(AGB). Based on an extensive literature review analysis, the most widely used surgery---Roux-en-Y gastric bypass surgery is not only make the obesity patients’weight reduce significantly, but also make more than80%of type2diabetes associated with obesity patients’ blood glucose and insulin long-term keep in the normal levels. Over the past60years, researchers have been trying to figure out the mechanisms and come up with various hypotheses, but these hypotheses did not interpret this phenomenon exactly. At present, the main mechanism that generally accepted by researchers including:(1) Reduced the food intake and absorption, thus reducing energy intake and glucose metabolism load;(2) Reduced the patient’s weight, and reduced the insulin resistance which caused by excess fat accumulation;(3)Gastrointestinal reconstruction changed the enteroinsluar axis hormone secretion, thereby improving glucose metabolism. Hormones which secreted from the gastrointestinal tract and which related to insulin and the insulin itself were known as "enteroinsluar axis". There are two hypotheses about the mechanisms of gastrointestinal hormone changes affect the insulin secretion.The first one is forgut hypothesis which thought that nutrients avoided to stimulate the stomach and duodenum, reduced the gastrointestinal tract to inhibit the secretion of the hormone insulin secretion and (or) synthesis, thus contributed to insulin synthesis and (or) release, and even increased insulinsensitivity.and the second one is hindgut hypothesis which thought that food entry into the distal jejunum or ileum ahead of time can promote insulin secretion and (or) of endocrine hormones enterogenic synthetic synthesis and (or secreted), thereby increased insulin synthesis and (or) release to improve the sensitivity to insulin in peripheral tissue.SIRT3is a member of Sirtuins family. Which is a mitochondrial nicotinamide adenine dinucleotide (NAD) dependent deacetylase.And mainly play an important role in regulating mitochondrial energy metabolism. Currently, researchers mainly concentrated the anti-aging effects of SIRT3enzyme for some studies have shown that SIRT3gene polymorphisms associated with longevity in genetically. Further, studies show that SIRT3can not only improve people’s obesity, but can also protect the cell which is lack of hypoxia-ischemia energy through improving the intracellular level of ATP.Human SIRT3have two forms of expression, one is a full-length protein with44kDa, and the other one is a short protein which missed the142-amino acid at the N-terminal. SIRT3was initially found in the mammalian mitochondria, expressed in brown adipose tissue and white adipose tissue, especially expressed higher in brown adipose tissue in which full of mitochondria. Subsequent studies found that, SIRT3also exists in the nucleus, but under certain conditions can be transferred from the nucleus to the mitochondria. For example, in the state of oxidative stress, the N-terminal signal peptide of SIRT3hydrolysis activated and transfer into mitochondria. SIRT3play an important role in the mitochondria as a deacetylase lysine acetylation in regulating the body’s mitochondria. In mammals, about20%of the mitochondrial protein was regulated rely on lysine deacetylation role which is much more than in the nucleus and the cytoplasm. Studies have shown that the mitochondrial protein will keep on acetylation state in mice which’s SIRT3been removed. SIRT3first time linked to the metabolism is because it can deacetylate acetyl coenzyme A (AceCS2) and enhance its activity. Acetyl coenzyme A is an intermediate product of many metabolic pathways, which shown that the SIRT3can regulate sugars, amino acids, fat metabolism and the TCA cycle. SIRT3overexpression in skeletal muscle and other tissues can be further explained its role, and this may become the new target to treat type2diabetes in human.70%of energy derived from fat catabolism in resting skeletal muscle, therefore, the SIRT3expression in the skeletal muscle has an important influence on fat metabolism. A recent study found that SIRT3enzyme reduced at least half in skeletal muscle of humans and animals with diabetes, and a view has been put forward that to increase the SIRT3enzyme expression should be able to improve the symptoms of diabetes.We recognize that gastric bypass can improve the symptoms of diabetes, however, whether gastric bypass has relationship with the SIRT3is still not known. Therefore, we designed this study attempt to explore this issue.Objective1、To establish the Roux-en-Y gastric bypass model in rat, and rat can survive at least four weeks after surgery.2、Detection and contrast the fasting blood glucose changes after Roux-en-Y gastric bypass in non-obese spontaneously type2diabetic rats (Goto-Kakizaki, GK rats). 3、To explore the changes and significance of the skeletal muscle SIRT3enzyme after Roux-en-Y gastric bypass in GK rats.Methods1、Use SD rats which is similar body type with GK rats to establish Roux-en-Y gastric bypass surgery model as pre-experiment.2、24GK rats were randomly divided into operation group (operation group OG group, n=8), sham group (sim-operation group SG group, n=8) and control group (control group CG group, n=8); OG group were subjected to gastric bypass surgery, SG rats underwent a sham surgery CG group for preoperative control OG group and SG groups before surgery,48h and1,2and4weeks of fasting blood glucose levels were measured.3、Surgical group and sham group GK rats were killed after4weeks, take thigh skeletal muscle to semi-quantitative measure the SIRT3enzyme values using western blot method; monitoring fasting blood glucose level of the control group and then killed after4weeks, using same method to measure thigh skeletal muscle SIRT3enzyme values.Results1、5of10SD rats successfully completed the Roux-en-Y gastric bypass surgery, and survived for more than four weeks.2、Fasting blood glucose level is similar to the three groups in the preoperative, postoperative surgical blood sugar levels decline, stabilize blood sugar levels after two weeks, compared with the sham group and the control group decreased significantly (P<0.05), sham group andcontrol group at each time of fasting blood glucose level was no significant difference (P>0.05).3、The surgery group skeletal muscle SIRT3enzyme expression was significantly increased compared with sham group and control group difference was significant (P<0.05).Conclusion1、In accordance with the literature experience, successfully established the Roux-en-Y gastric bypass model in rat. 2、For the first time to explore the relationship between gastric bypass surgery and skeletal muscle SIRT3enzyme.3、Our results suggest that the Roux-en-Y gastric bypass surgery can significantly decrease the fasting blood glucose in GK rats, and skeletal muscle SIRT3enzyme expression was significantly increased after4weeks, which may be one of the mechanisms in improving diabetes. |
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