Investigation Of Multi-organ Morphology In Insulin Resistant Rats At Normal Blood Glucose Stage

Research backgroundType 2 diabetes mellitus(T2DM) is a kind of common endocrine and metabolic diseases.The morbidity, mortality and mutilation rate are very high that serious harm to human health. Insulin resistance (IR) is the invasion of T2DM pathophysiological basis. In 1995 Stern introduced the famous"common soil"doctrine,considering diabetes mellitus(DM),hypertension,coronary heart disease, abnormal lipid metabolism, and obesity were"growth"in comitant soil—insulin resistance.It demonstraed that insulin resistance was a common pathopoiesis factor for these diseases.IR is more than physical need of insulin in the effector organ produce physiological effects. Insulin resistance can lead to the persistence of abnormal glucose tolerance and diabetes.DM is an important reason which cause end-stage renal disease, blindness, non-traumatic amputation. DM chronic complications impact the quality of life for patients, their families and raise society heavy burden. Our original research indicated that both high-sugar-fat (2H) and high-sugar-fat-salt (3H) diets induced insulin resistance model in rats successfully. During the period of insulin resistance with normal blood glucose, peripheral neuropathy has already developed.We surmised that at normal blood glucose stage before diabetes, multi-organ pathological changes already exist. Therefore, on the basis of inducing rat model with insulin resistance successfully,we studied the morphological changes of multiple organs at the stage of euglycemia,and approached the relation between morphological changes and diabetes complicated organs damage.AIMIn the successful establishment of IR with normal blood sugar rat model,we observed the morphologic structure changes of kidney, lens and liver. Designed to provide experimental basis for pervention of organs damage caused by diabetes and provide theoretical evidence for the treatment of prediabetes.METHODSMake IR rat model successfully,we adopted light microscopy, transmission electron microscopy(TEM) and scanning electron microscopy(SEM) techniques to study the morphologic changes of kidney, lens and liver.RESULTS1. 2H group:Glomerulus basement membrane and renal tubular basement membrane were thickening respectively (2.23±0.88)μm,(0.86±0.25)μm,P<0.01, mesangial region is widening and foot process turned turgescence and meromixis, endodermis fenestra disappeared partly. Filtration barrier construction was destroyed. Kidney interstitial became edema, infiltrated by inflammation cells;Foot process mixed together, and cell body broadened. 3H grope: Glomerulus and renal tubular basement membrane changed thick respectively (1.88±0.41)μm , (0.96±0.22)μm , P < 0.01, foot process turned turgescence,mixed together mainly , endodermis fenestra disappeared mostly. Filtration barrier construction was destroyed severely. Kidney interstitial became edema, infiltrated by inflammation cells;Glomerulus enlarged,renal tubule epithelium had a great quantity of lipid droplet to deposit. In addition, there were plasmocyte and myeloid body in renal interstitium;Renal tubule brush border aligned untidily, microvillus were lodging and lumens crimpled. Some of the cells degenerated and desquamated, tubal wall was hollow. Foot process mixed together mostly and cell body broadened obviously,slit pore vanished almostly. 2. Under TEM observing, 2H group,lens fibrocyte mitochondria dissolved and disrupted. The cristae disappeared as well as turned into vacuolization. Fat deposition was found in the cytoplasm;And 3H group, the gap junction was destroyed,the fibrocyte interspace broadened,and there was fat deposited.Under SEM observing, 2H and 3H group superficial cortical layer fibrocytes degenerated, their shape and arrangement were irregular; The volume of fibrocytes increased,a great of fibrocytes fused;The deep cortical layer fibrocyte was abnormal;The interspace of eye lens fibrocyte extended remarkably.3. 2H group appeared diffuse hepatocyte steatosis and inflammatory cell infiltrated in hepatic lobule. Stained red proliferated collagen fibers were observed surrounding hepatic sinusoid and portal areas. 3H group showed that hepatic cord arrange irregularly. Liver cell had pointing necrosis, inflammatory cell infiltrated. Diffuse hepatocyte steatosis and lipofuscin deposition displayed in hepatocyte, lipid droplets were different in size. Proliferated collagen fibers were seen between consecutive hepatocytes and around hepatic sinusoid and portal areas. TEM demonstrated that Kupffer cells increased and many various lipid droplets displayed in hepatocytes of 2H and 3H groups. Proliferated collagen fibers were seen frequently in Disse space. Lymphocytes and plasma cells activated and proliferated. Moreover, plasma cells and hepatic stellate cells (HSC) contacted tightly.CONCLUSION1. IR rats present kidney morphologic changes at normal blood glucose stage. The glomerular filtration barrier and renal tubule exist pathological changes,and it may be the pathological basis to pose diabetic nephropathy.2. IR rats present lens ultrastructural changes at normal blood glucose stage,it is of possibility to develop cataract.3. Early hepatic fibrosis is found in IR rats at normal blood glucose stage. It may be associated with activation of immune system.