OBJECTIVETo compare the retinal function and retinal vascular pathologies in C57BL/6 and eNOS-knockout (eNOS(-/-)) mouse models of type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ).

METHODST1DM models were established in 6- to 8-week-old C57BL/6 and eNOS(-/-) mice by intraperitoneal STZ injection. Electroretinogram (ERG) examination, fluorescein angiography (FFA), immunofluorescence staining and retinal ganglion cell counts were carried out before and after STZ injection.

RESULTSDiabetic C57BL/6 and eNOS(-/-) mice showed significantly lowered a-wave and b-wave amplitude in ERG and reduced number of retinal ganglion cells (P<0.05), and the retinal vessels in diabetic eNOS(-/-) mice became tortuous. Compared with diabetic C57BL/6 mice, diabetic eNOS(-/-) mice showed more severe pathological changes in retinal function and retinal vessels with also more rapid onset of pathologies.

CONCLUSIONCompared with C57BL/6 mouse models, eNOS(-/-) mouse models of T1DM can better represent the occurrence and development of diabetic retinopathy, thus providing an ideal model for diabetes and diabetic retinopathy studies.

Animals ; Diabetes Mellitus, Experimental ; complications ; pathology ; Diabetes Mellitus, Type 1 ; complications ; pathology ; Diabetic Retinopathy ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nitric Oxide Synthase Type III ; genetics ; Retinal Ganglion Cells ; pathology

OBJECTIVETo investigate the perfusion restoration of type 1 diabetic mouse under the setting of surgically induced hind limb ischemia and the number and function of bone marrow endothelial progenitor cells (EPCs).

METHODSForty mice were randomly divided into two groups: one group was injected with alloxan through tail vein to induce type 1 diabetes mellitus, and another group was set as control group. All mice were surgically induced to hind limb ischemia. Blood flow was monitored with Laser Doppler perfusion imaging for 4 weeks after artery ligation. Ten mice in each group were sacrificed and muscle tissues were harvested for histological detection. The remaining mice were sacrificed 7 days after surgery, bone marrow mesenchymal stem cells were harvested and EPCs were analyzed by flow cytometry and then were collected to culture for functional detection.

RESULTSAll mice received alloxan injection showed typical symptoms of type 1 diabetes mellitus. Restoration of blood flow was significantly slower in type 1 diabetic mice with lower level of vascular density in ischemic muscles than control group (P < 0.001, P < 0.05). The number and function of EPCs (CD34 and vascular endothelial growth factor receptor 2 double positive cells) in type 1 diabetic mice were significantly lower than that in control mice (P < 0.05).

CONCLUSIONSThe spontaneous angiogenesis is attenuated with a decreased number and function of EPCs in the setting of type 1 diabetes mellitus. This may partly explain why diabetic patients with peripheral artery diseases have more aggressive disease and poorer outcome.

Animals ; Antigens, CD34 ; analysis ; Cell Count ; Diabetes Mellitus, Experimental ; complications ; pathology ; Diabetes Mellitus, Type 1 ; complications ; Hindlimb ; blood supply ; Ischemia ; complications ; physiopathology ; Mesenchymal Stromal Cells ; chemistry ; Mice ; Reperfusion ; Vascular Endothelial Growth Factor Receptor-2 ; analysis

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8+/-3.9 vs. 11.1 +/-1.9%, p<0.001) and increased IMT (0.51+/-0.10 vs. 0.42+/-0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1+/-2.5 vs. 9.9+/-3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications.
Adult ; Diabetes Mellitus, Type 1/*complications ; Diabetic Angiopathies/*etiology ; Endothelium, Vascular/*physiology ; Female ; Humans ; Male ; *Microcirculation ; Tunica Intima/pathology ; Tunica Media/pathology ; Vasodilation

This article reviews the clinical and experimental researches on cognitive impairment related to diabetes in the recent decade. Most clinical studies indicate that the cognitive impairment in patients with type 1 diabetes mellitus is related to recurrent hypoglycemia closely. There is little research about whether or not hyperglycemia is related to cognitive impairment in patients with type 1 diabetes mellitus. Most studies indicate that the cognitive impairment in type 2 diabetes involves multiple factors through multiple mechanisms, including blood glucose, blood lipid, blood pressure, level of insulin, medication, chronic complication, etc. But, there has been no large-scale, multi-center, randomized controlled clinical trial in China recently. And what is more, some problems exist in this field of research, such as the lack of golden criterion of cognitive function measurement, different population of studied objects, and incomprehensive handling of confounding factors. Experimental studies found that hippocampal long-term potentiation (LTP) was impaired, which were manifested by impairment of spatial memory and decreased expression of LTP, but it's relation to hyperglycemia, the duration of diabetes, learning and memory has always been differently reported by different researches. Thus, there are a lot of unknown things to be explored and studied in order to clarify its mechanism. TCM has abundant clinical experience in treating cerebral disease with medicine that enforces the kidney and promotes wit. However, there has been no research on treating diabetic cognitive impairment, which requires work to be done actively and TCM to be put into full play, in order to improve the treatment of diabetes and enhance living quality of patients.
Animals ; Cognition Disorders ; etiology ; pathology ; physiopathology ; Diabetes Mellitus, Experimental ; pathology ; physiopathology ; psychology ; Diabetes Mellitus, Type 1 ; pathology ; physiopathology ; psychology ; Diabetes Mellitus, Type 2 ; pathology ; physiopathology ; psychology ; Drugs, Chinese Herbal ; therapeutic use ; Hippocampus ; pathology ; physiopathology ; Humans ; Hyperglycemia ; complications ; Hypoglycemia ; complications ; Long-Term Potentiation ; Neuronal Plasticity

Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review.
Acute Disease ; Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Delayed Diagnosis ; Diabetes Mellitus, Type 1/complications/*pathology ; Diagnostic Errors ; Female ; Glycogen Storage Disease/complications/*diagnosis/ultrasonography ; Hepatitis/diagnosis ; Hepatomegaly/complications/*diagnosis/ultrasonography ; Humans ; Liver/pathology ; Recurrence ; Young Adult

OBJECTIVETo explore the effects and underlying mechanisms of Panax notoginoside (PNS) on the nephropathy in rats with type 1 diabetes.

METHODSA murine model of diabetic nephropathy was set up by an intravenous injection of streptozotocin (STZ). Wistar rats were randomly divided into 5 groups: the control group, the diabetic group (DM), the group treated with low-dosage PNS (PNS-L), the group treated with high-dosage PNS (PNS-H) and the group treated with catopril. Rats in the PNS-L and PNS-H groups were given different dosages of PNS while rats in the catopril group were given catopril through gastrogavage every day for the next four consecutive weeks. Serum creatinine (Cr) levels, endogenous creatinine clearance rate (CCr), and 24-h urinary microalbumin (UAlb) were examined and calculated. Meanwhile, immunohistochemistry was applied to determine the expression of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-7 (BMP-7) in the kidney tissue.

RESULTSThe levels of Cr, Ccr, and UAlb were all elevated significantly in the DM group (P<0.01). The expression of VEGF protein was increased but BMP-7 protein was decreased in the kidney tissue (P<0.01). However, the above items decreased in the PNS-L, PNS-H and catopril groups compared with the DM group (P<0.05, P<0.01). In the PNS-L, PNS-H and catopril groups, the expression of VEGF protein was decreased but BMP-7 protein was increased in the kidney tissue (P<0.05, P<0.01).

CONCLUSIONPNS shows protective effects on the kidney in type 1 diabetic rats at the early stage. The protective mechanism might be closely related to its role of inhibiting the expression of VEGF protein and enhancing the expression of BMP-7 protein in the kidney.

Animals ; Body Weight ; drug effects ; Bone Morphogenetic Protein 7 ; metabolism ; Diabetes Mellitus, Type 1 ; complications ; drug therapy ; pathology ; physiopathology ; Diabetic Nephropathies ; complications ; drug therapy ; pathology ; physiopathology ; Hypertrophy ; Immunohistochemistry ; Kidney ; drug effects ; metabolism ; pathology ; Kidney Function Tests ; Male ; Panax ; chemistry ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Proteinuria ; complications ; drug therapy ; pathology ; physiopathology ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUNDThe development of diabetic cardiomyopathy is multifactorial. Insulin resistance (IR) and excessive activity of the renin-angiotensin system are confirmed reasons for diabetic cardiomyopathy. Renin-angiotensin system (RAS) inhibitors can reduce tissue Ang II levels, with beneficial effects on cardiovascular function. Therefore, in type-2 diabetes mellitus (T2DM), blockade of the RAS may have the function of protecting against diabetic cardiomyopathy through increasing insulin sensitivity and inhibiting excessive activity of RAS. However, this has not been confirmed.

METHODSThe effect of valsartan, an angiotensin receptor blocker (ARB), on diabetic cardiomyopathy in the presence of T2DM was studied. Wistar rats with T2DM and T2DM treated with valsartan were studied. Glucose infusion rates (GIR), index of IR, heart weight, the heart weight-to-body weight ratio (HW/BW), myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type I and collagen type III content were measured.

RESULTSGIR in T2DM rats and T2DM rats treated with valsartan decreased (P < 0.01). In T2DM rats treated with valsartan, heart weight, myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type I and collagen type III content were higher than in control rats, but lower than in T2DM rats. In rats with T2DM, GIR was negatively and significantly correlated with all the variables. However, in T2DM rats treated with valsartan or normal control rats, none of the correlations was significant.

CONCLUSIONSIn the presence of T2DM, diabetic cardiomyopathy is related with IR. Valsartan can not alleviate IR, but can protect against diabetic cardiomyopathy and remove the correlation between IR and diabetic cardiomyopathy.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Apoptosis ; Collagen Type I ; analysis ; Collagen Type III ; analysis ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Diabetic Cardiomyopathies ; prevention & control ; Hydroxyproline ; analysis ; Insulin Resistance ; Male ; Myocardium ; chemistry ; pathology ; Rats ; Rats, Wistar ; Tetrazoles ; therapeutic use ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan