No abstract available.
Adipocytes ; Estradiol ; Rats, Inbred OLETF

OBJECTIVES: Type 2 diabetes mellitus (T2DM) increases fracture risk despite normal to high levels of bone mineral density. Bone quality is known to affect bone fragility in T2DM. The aim of this study was to clarify the trabecular bone microstructure and cortical bone geometry of the femur in T2DM model rats. METHODS: Five-week-old Otsuka Long-Evans Tokushima Fatty (OLETF; n = 5) and Long-Evans Tokushima Otsuka (LETO; n = 5) rats were used. At the age of 18 months, femurs were scanned with micro-computed tomography, and trabecular bone microstructure and cortical bone geometry were analyzed. RESULTS: Trabecular bone microstructure and cortical bone geometry deteriorated in the femur in OLETF rats. Compared with in LETO rats, in OLETF rats, bone volume fraction, trabecular number and connectivity density decreased, and trabecular space significantly increased. Moreover, in OLETF rats, cortical bone volume and section area decreased, and medullary volume significantly increased. CONCLUSIONS: Long-term T2DM leaded to deterioration in trabecular and cortical bone structure. Therefore, OLETF rats may serve as a useful animal model for investigating the relationship between T2DM and bone quality.
Animals ; Bone Density ; Diabetes Mellitus, Type 2 ; Femur ; Models, Animal ; Rats* ; Rats, Inbred OLETF

OBJECTIVETo investigate the relationship between visceral fat depot and adiponectin level in OLETF rats.

METHODSTwenty male OLETF rats and 10 male Long-Evans Tokushima Otsuka (LETO) rats were subjected to regular oral glucose tolerance test (OGTT). The rats were sacrificed at the ages of 8, 32 and 40 weeks for measurements of the body weight, blood glucose, blood lipid level, blood insulin, and weight of the visceral fat.

RESULTSCompared with LETO rats, OLETF rats had significantly higher body weight and visceral fat with impaired glucose tolerance (P<0.05). OLETF rats also had higher blood insulin, TG, FFA and CHOL levels (P<0.05). The plasma adiponectin level was significantly lower in OLETF rats than in LETO rats at different ages (P<0.05). The adiponectin mRNA level in the adipose tissue of OLETF rats was comparable with that in LETO rats, but significantly decreased at 32 and 40 weeks of age (P<0.01).

CONCLUSIONPlasma adiponectin level is significantly correlated to insulin sensitivity and visceral fat depots in OLETF rats, but a lowered APN mRNA expression level is not the main reason for a decreased plasma adiponectin level in the early stage.

Adiponectin ; blood ; genetics ; metabolism ; Animals ; Insulin Resistance ; Intra-Abdominal Fat ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred OLETF

BACKGROUND: Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals. METHODS: We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment. RESULTS: Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group. CONCLUSION: Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.
Animals ; Body Composition ; Diabetes Mellitus, Type 2 ; Exercise* ; Fasting ; Glucose* ; Metabolism* ; Rats, Inbred OLETF* ; Thiazolidinediones ; Weight Gain

OBJECTIVETo investigate the association between plasma adiponectin and insulin resistance in OLETF rats.

METHODSTwenty male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and 10 male Long-evans Tokushima Otsuka (LETO) rats underwent oral glucose tolerance test (OGTT) at 13 and 40 weeks of age. At 8, 32 and 40 weeks of age, the rats were sacrificed to measure the blood glucose, plasma insulin and adiponectin levels, and serum levels of TG, CHOL and FFA.

RESULTSThe plasma adiponectin level was significantly decreased in 8-week-old OLETF rats compared with that of LETO rats (P<0.05). The plasma insulin level, TG, CHOL, and FFA were significantly higher in OLETF rats than in LETO rats at 32 and 40 weeks of age.

CONCLUSIONA decreased plasma level of adiponectin preludes insulin resistance and is inversely correlated to insulin sensitivity. Hypoadiponectinemia may be an important reason leading to insulin resistance.

Adiponectin ; blood ; Animals ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; Insulin ; pharmacology ; Insulin Resistance ; Male ; Rats ; Rats, Inbred OLETF ; Rats, Long-Evans

PURPOSE: Erectile dysfunction commonly occurs in men with diabetes mellitus. Nitric oxide synthase (NOS) is essential for regulation of penile erection, and the isoforms of NOS have significance in a variety of complications of diabetes. However, little is known about the localization, abundance, and changes in NOS in diabetes. Therefore, we characterized the localization and abundance of NOS isoforms and explored their relationships and how they are altered in diabetes. MATERIALS AND METHODS: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, which models type II diabetes mellitus, and the non-diabetic control Long-Evans Tokushima Otsuka (LETO) rat were used. We analyzed the distribution of NOS isoforms in the isolated corupus cavernosum of both LETO and OLETF rats by immunohistochemistry (IHC). The mRNA expression of NOS isoforms was also analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The concentration of nitrite/nitrate in cavernosal homogenate was higher in diabetic rats than non-diabetic rats, but the difference was not statistically significant. There was a reduction of immunoreactivity for nNOS and eNOS as well as nNOS and eNOS mRNA expression (p<0.05) in diabetic rats, compared to non-diabetic rats. In contrast, the IHC stain showed that iNOS increased in both the endothelium and vascular smooth muscle in the diabetic rats, and the mRNA expression of iNOS gene was also up-regulated (p<0.05). CONCLUSIONS: Change in the activity levels of NOS isoforms within the corpus cavernosum could be a major source of pathogenesis of erectile dysfunction in diabetes mellitus.
Animals ; Diabetes Mellitus ; Endothelium ; Erectile Dysfunction ; Humans ; Immunohistochemistry ; Male ; Muscle, Smooth, Vascular ; Nitric Oxide Synthase* ; Nitric Oxide* ; Penile Erection ; Protein Isoforms ; Rats* ; Rats, Inbred OLETF ; RNA, Messenger

BACKGROUND: 17 beta-estradiol is known to play an important role in glucose homeostasis. Lipin-1 is a nuclear protein that is essential in adipocyte differentiation and it is considered to play a role in ectopic fat deposition and the redistribution of fat. The aim of this study was to evaluate the effect of 17 beta-estradiol on the lipin-1 expression in the adipocytes of OLETF rats, which is an animal model of diabetes. METHODS: The OLETF rats were divided into 3 groups, 1) the sham-operation group (SHAM) 2) the castrated group (CAST) and 2) the castrated and estradiol treatment group (EST), and all the rats were at 6 weeks of age. LETO rats were used as a control group (LETO). 0.1 mg of estradiol valerate was injected subcutaneously every 4 weeks in the rats of the EST group. The visceral and subcutaneous tissues were isolated to evaluate the lipin-1 protein expression. The lipin-1 expression was measured in human visceral and subcutaneous preadipocytes. RESULTS: Less body weight gain was observed in the EST group compared with that of the SHAM group. In addition, improvement in the glucose tolerance was observed in the EST group. The lipin-1 expression in visceral fat was decreased in the SHAM and CAST groups, but it was but recovered in the EST group. The lipin-1 expression in the subcutaneous fat was decreased in the SHAM, CAST, and EST groups. CONCLUSION: Long term estradiol treatment in OLETF rats reduces the body weight gain and improves the glucose tolerance. Estradiol enhances the lipin-1 protein expression in the visceral adipocytes, but not in the subcutaneous adipocytes.
Adipocytes ; Animals ; Body Weight ; Estradiol ; Glucose ; Homeostasis ; Humans ; Intra-Abdominal Fat ; Models, Animal ; Nuclear Proteins ; Rats ; Rats, Inbred OLETF ; Salicylamides ; Subcutaneous Fat ; Subcutaneous Tissue

PURPOSE: To compare retinal ultra-structures of diabetic rats (OLETF, Otsuka Long-Evans Tokushima Fatty) with those of agematched non-diabetic rats (LETO, Long-Evans Tokushima Otsuka) using transmission electron micrography (TEM). METHODS: The body weights and blood sugar levels of the OLETF rats and LETO rats (n=5) were measured at 10 and 50 weeks of age. Using a TEM, we compared the ultra-structural changes between the retinas of the 50-week-old OLETF and LETO rats. We analyzed the sizes of the pericytes and the thicknesses of the retinal capillary basement membranes between the two groups. Comparisons were made using a Scion Image(R). RESULTS: The mean body weight and blood sugar levels of the 50-week-old OLETF rats were significantly higher than those of the LETO rats (p(R)0.05). The thicknesses of the retinal capillary basement membranes in the outer plexiform layer and the size of pericytes were significantly increased in the OLETF rats at 50 weeks of age (p<0.05). The number of nuclei in the inner nuclear layer and the outer nuclear layer (photoreceptor cell nuclei) significantly decreased (p<0.05). However, the height of the RPE cells and basal in-foldings showed no significant differences between the OLETF and LETO rats. CONCLUSIONS: The retinal changes in the OLETF rats were observed relatively early at 50 weeks of age. These changes are similar to those seen in human diabetic retinopathy. Change in the capillaries is one feature of early retinal change. OLETF rats may be a useful animal model in NIDDM to examine diabetic retinal changes.
Animals ; Basement Membrane ; Blood Glucose ; Body Weight ; Capillaries ; Diabetes Mellitus, Type 2 ; Diabetic Retinopathy ; Electrons ; Humans ; Microscopy, Electron ; Models, Animal ; Pericytes ; Rats ; Rats, Inbred OLETF ; Retina ; Retinaldehyde

PURPOSE: It is reported that 65% of diabetic male patients over 60 of their age are impotent. However, there is no report concerning the effect of serum glucose control on erectile dysfunction in diabetic patient. This study was performed to evaluate the effects of serum glucose control on erectile dysfunction. MATERIALS AMD METHODS: The development of Diabetes mellitus was defined that the serum glucose level was above 200mg/dL in random test at 25 weeks. We designed the experimental specimen into 3 groups; group I: diabetic OLETF (Otsuka Long Evans Tokushima Fatty) rats without blood sugar control (n=10), group II: diabetic OLETF rats with blood sugar control with 4U insulin subcutaneous injection daily from 26 to 46 weeks (n=10), group III: diabetic OLETF rats with blood sugar control with 10U insulin subcutaneous injection daily from 26 to 46 weeks (n=10). We estimated the collagen content of penile tunica albuginea with the scanning electron microscopy and observed the endothelial layers of corpus cavernosum with the transmission electron microscopy in each group. RESULTS: The serum glucose level was 249 +/- 4.1mg/dL, 234 +/- 2.7mg/dL, 215 +/- 3.0mg/dL respectively in group I, II, III, and decreased in order of group II, III. The differences among groups were statistically significant (p<0.05). The thickness of collagen bundles of penile tunica albuginea was 0.98 +/- 0.1 micrometer, 0.94 +/- 0.3 micrometer, 0.92 +/- 0.1 micrometer respectively in group I, II, III, and decreased in order of group II, III. The differences among groups were statistically significant (p<0.05). The endothelial layers of corpus cavernosum were decreased in II, III. CONCLUSIONS: The serum glucose control in diabetic rats decreases the collagen con tents in penile tunica albuginea and the endothelial layers of corpus cavernosum.
Animals ; Blood Glucose* ; Collagen* ; Diabetes Mellitus ; Endothelium ; Erectile Dysfunction ; Humans ; Injections, Subcutaneous ; Insulin ; Male ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Rats* ; Rats, Inbred OLETF

PURPOSE: To evaluate the changes in corneal fine structure of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, compared with age-matched nondiabetic rats. METHODS: At the ages of 30 and 50 weeks, we measured the body weight and blood glucose level of OELTF and control rats (n=5 in each age-matched group). Using the transmission electron micrography (TEM), we examined the ultrastructural changes between the corneas of 30-and 50-week-old OLETF and control rats. RESULTS: At the age of 30 and 50 weeks, the mean body weight and blood glucose levels of OLETF rats were significantly higher than those of control rats (p<0.05). The area of basement membrane occupied by hemidesmosome decreased significantly in OLETF rats at the ages of 30 and 50 weeks compared with control rats (p<0.001). In TEM, the corneas of OLETF rats showed irregular, thick basement membranes thin hemidesmosomes and decreased anchoring fibrils formation, compared with control rats. There was no significant difference of Descemet's membrane thickness between OLETF and control rats (p>0.05). CONCLUSIONS: The author could observe the changes of the corneal adherent complex and basement membrane in OLETF rats, a new strain of spontaneous non-insulin dependent diabetes mellitus (NIDDM) model. OLETF rats may be useful as an animal model of NIDDM to examine the diabetic corneal changes.
Animals ; Basement Membrane ; Blood Glucose ; Body Weight ; Cornea* ; Descemet Membrane ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Hemidesmosomes ; Models, Animal ; Rats* ; Rats, Inbred OLETF