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The Effect of Hypertension on the Islet Microvascular Density and Beta-cell Function in Rats

Author: ZhangJiJia
Tutor: TianChenGuang
School: Zhengzhou University
Course: Internal Medicine
Keywords: Hypertension Microvascular density Pancreas islet function
CLC: R587.1
Type: Master's thesis
Year: 2013
Downloads: 11
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Abstract


Background and ObjectiveDiabetes is a kind of chronic progressive metabolic disease which is characterized by chronic hyperglycemia, it is due to the dysfunctional secretion and (or) effect of insulin. Glucotoxicity and lipotoxicity, which caused by long-term rise of blood sugar and blood lipid, lead to the dysfunction and failure of heart, eyes, kidneys, vessels, the nervous system and other tissues and organs. Compared with non-diabetic patients, diabetic patients have a higher prevalence rate, younger age of onsets and more rapid progression in atherosclerosis. The incidence of hypertension is significantly higher than the non-diabetic population.The primary hypertension is a kind of syndrome which is characterized by blood pressure rise with or without many cardiovascular risk factors. The patients of hypertension in China amounted to330million in2010, with a prevalence rate of33.5%. The heart and blood vessels is a major target organ of hypertension. No significant pathological changes occur in the early stage of hypertension, whereas long-term hypertension can cause serious systemic small artery lesions, mainly in the narrowing of the lumen diameter, resulting in ischemia of important target organs such as the heart, brain and kidney, and there is a microvascular rarefaction and distortion. Vascular damage is systemic, so all the organs and tissues in the body will be involved in different degrees in theory. The pancreas islet as an endocrine organ of the human body is rich in blood supply. Epidemiological data indicated that patients with hypertension suffered from diabetes compared to health persons is2-3times higher in prevalence, suggesting that hypertension is likely to cause pancreas islet damage. If hypertension causes islet dysfunction due to vascular damage, pancreas may be one of the target organ of hypertension.The pathogenesis of diabetes mellitus and hypertension has been studied for a long time. There are several mechanisms, such as insulin resistance, endothelial dysfunction, sodium retention and increased sympathetic nerve tension that are considered to be responsible for their complications. However, with the detection of the mRNA of RAS members including Angiotensin (Ang)1a/1b, Ang Ⅱ and renin in pancreatic acinar cells in1991, the affect of islet function by hypertension takes researcher’s attention gradually. Studies have found that Ang Ⅱ receptors1(AT1R), Ang Ⅱ receptor2(AT2R), ACE and angiotensinogen express in islets in rats, AT1R was also detected in the membrane and cytoplasm of beta cells. All of these results suggested that Ang Ⅱ may have paracrine effect, or play a role in the regulation of intracellular. Activated RAS system can affect insulin synthesis and secretion by regulating the contraction of islet microvascular, reducing the synthesis of preproinsulin, increasing islet fibrosis, and lead to islet dysfunction. In addition, hypertension increases the oxidative stress, then causing the islet tissue injury and islet dysfunction. However, research about the relationship between microcirculation and islet function is few.The islet blood circulation is very rich. Vascular density of islet is five times higher than the exocrine part of the glands. It receives approximately5-15%of pancreatic blood flow, while taking only1%of the pancreas volume. The pancreatic microcirculation participates in information transmission, material and energy exchange between cells and tissues. It is the basic environment for islet cells to maintain function, so the impaired pancreatic microcirculation is bound to affect islet function.Studies have found that, if given early anti-hyperglycemic therapy, the high blood pressure of the islet microcirculation of diabetic rats can be reversed, while the blood pressure of the islet microcirculation of normal rats will rise after glucose load. We may suggested that high perfusion of the islet microcirculation is a compensatory process for the increased islet function in the pre-diabetes period, but it will may cause high blood pressure of islet microcirculation and islet endothelial cell damage in a long-term. And it will eventually lead to the islet microcirculation hypoperfusion and decompensation. Pancreatic microcirculation may be a key factor in islet β-cell structure changes and functional damage.In this experiment we choose the SHR rats to measure the microvascular density of islet and to evaluate the function of the microcirculation. The aim is to discuss the relationship between hypertension and islet function, and to explore a new way of understanding the pathogenesis and treatment of diabetes.Methods(1) Group settingWe have set4groups in this experiment. They are SHR rats at12-weeks (12w-SHR), SHR rats at24-weeks (24w-SHR) as experiment groups, Wistar rats at12weeks (12w-control) and at24weeks (24w-control) as normal control groups. Each group has10rats. Each group had adaptive feeding for one week before the test.(2) ObservationsAfter adaptive feeding for one week in all groups, intravenous glucose tolerance test and intravenous insulin release test were taken, and part of the pancreatic tissues were taken for HE staining to observe changes in islet morphology, the others were for immunohistochemistry staining to calculate microvascular density and the relative insulin levels.(3) Statistical methodsThe groups were compared using analysis of variance (one-way ANOVA); the difference between two groups were compared using the least significant difference (LSD) method, P<0.05was considered statistically significant. Results(1) IVGTTThere was no significant difference between the control group and the SHR group in the fasting blood sugar level. Compared with Wistar rats, the blood glucose level of SHR rats at the same age were higher at5min,10min and30min, and the difference was statistically significant (P<0.05); while there was no significant difference (P>0.05) at60min.(2) IVIRTBasal insulin (Omin) of SHR rats at24weeks was higher than the same week-old Wistar rats, the difference was statistically significant (P<0.05). SHR rats had a insulin secretion peak delay, at which24w-SHR group peak postponed to10min. Insulin secretion began to decline at10min, but the control group rats decreased faster than the same week-old SHR rats, and the difference was statistically significant (P <0.05). Insulin secretion of control rats was still slightly lower than the same week-old SHR rats at60min, the difference was statistically significant (P<0.05).(3) HE stainingControl group rats had a clear islet structure, and a intact boundary. The islet cells arranged in neat rows and had no morphological abnormalities. The SHR group islet increased significantly, and had internal bleeding, but still arranged in neat rows and had no morphological abnormalities.(4) Insulin stainingThere was no difference between the optical density of insulin stained positive regional of control rats of different ages (P>0.05). Compared SHR rats with the week-old control rats, the optical density of positive regional was significantly higher, and the difference was statistically significant (P<0.05). And as SHR rats increases with age, the optical density of positive regional showed a growing trend, and the difference was statistically significant (P<0.05). (5) Microvascular density (MVD)Compared to the control group rats, microvascular density of SHR rats at12weeks decreased by48%, the difference was statistically significant (P<0.05), while microvascular density of SHR rats at24weeks decreased by75%, the difference was statistically significant (P<0.05).Conclusions(1) Hypertension decreased pancreas islet microvascular density in SHR rats.(2) Hypertension affected pancreas islet function, in particularly, the first phase insulin secretion has been delayed.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetes
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