Search

We studied the difference in the susceptibility to neonatal streptozotocin (STZ) diabetes between spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Two-day-old female SHR and WKY were injected intraperitoneally with 75.0 mg/kg of STZ or vehicle for control. Hyperglycemia developed in both strains at 4 days of age, but SHR were more hyperglycemic. Overt hyperglycemia developed in SHR with aging after a partial recovery from initial hyperglycemia at 10 days of age, whereas WKY did not develop significant hyperglycemia except shortly after STZ treatment. Percentage of insulin-positive B cells in total islet cells and pancreatic immunoreactive insulin (IRI) content were measured at 4 days, 10 days, 4 weeks, and 12 weeks of age. B cells per islet and pancreatic IRI content were significantly reduced in STZ-treated groups as compared with control in both SHR and WKY at 4 days of age, but later they increased significantly with aging in both strains. However, the reduction in pancreatic IRI content relative to control was significantly greater in SHR than in WKY from 4 days (−94.5 ± 3.5, −84.1 ± 4.8; p< 0.01) to 12 weeks (−97.1 ± 2.1, −28.0 ± 2.5; p< 0.05), and the reduction in B cells per islet was also greater in SHR at 4 weeks of age. These results indicated that the initial destruction of pancreatic B cells induced by STZ was greater, and the following regeneration was less in SHR than in WKY. The association of the susceptibility to neonatal STZ diabetes with the development of genetic hypertension in SHR remained to be elucidated.

We examined the blood pressure changes in hypertensive and normotensive rats with Type 2 diabetes induced by neonatal streptozotocin (STZ) treatment. STZ was intraperitoneally injected at 2 days of age with the dose of 25, 50 and 75 mg/kg for male spontaneously hypertensive rats (SHR) and with 75, 100, 125 and 150 mg/kg for male normotensive Wistar Kyoto rats (WKY), Blood pressure was measured by indirect tail-cuff method until 12 weeks of age. STZ-treated SHR, of which plasma glucose and glycosylated hemoglobin increased and body weight decreased with the dose of STZ, deve loped and maintained hypertension, same as did the vehicle-treated control SHR, On the other hand, STZ-treated WKY which developed only mild hyperglycemia lost body weight with the dose of STZ but the blood pressures rose slightly, these changes being correlated with the glycemic levels. The explanation for these differences between SHR and WKY remained to be elucidated.

In an effort to elucidate the mechanism of calmodulin regulation of muscle contraction, we investigated the interaction between calmodulin and troponin components in the presence of Ca2+ or Sr2+ by the use of ultracentrifugation methods and polyacrylamide-gel electrophoresis. Skeletal-muscle troponin C bound to troponin I and dissociated it from the tropomyosin-actin complex in the presence of Ca2+ or Sr2+. When troponin T was absent, calmodulin bound to troponin I and dissociated it from the tropomyosin-actin complex in the presence of Ca2+ or Sr2+. When troponin T was present, calmodulin hardly bound to troponin I even in the presence of bivalent cations. Trifluoperazine, a calmodulin antagonist, inhibited the bivalent-cation-dependent interaction between calmodulin and troponin I. Calmodulin migrated more slowly in the presence of Sr2+ than it did in the presence of EGTA but faster than it did in the presence of Ca2+ on polyacrylamide-gel electrophoresis under non-denaturing conditions. It is concluded that troponin T is not required in the calmodulin regulation of muscle contraction because troponin T inhibits the bivalent-cation-dependent interaction between calmodulin and troponin I and because calmodulin binds to troponin I and dissociates it from the tropomyosin-actin complex in a bivalent-cation-dependent manner. Sr2+-induced exposure of the hydrophobic region enables calmodulin to bind to troponin I, as is the case with Ca2+.

This study was designed to develop an animal model of Type 2 (non-insulin-dependent) diabetes with persistent hypertension. Male spontaneously hypertensive rats were treated with 25.0, 37.5, 50.0, 62.5 or 75.0 mg/kg of streptozotocin given intraperitoneally at 2 days of age and maintained for 12 weeks. In the rats which received 50.0 mg/kg or more streptozotocin, overt hyperglycaemia gradually and consistently developed following incomplete recovery from an initial hyperglycaemia. Compared to vehicle-treated controls, body weight gain in these animals did not differ for the first 8 weeks; thereafter, it was slightly but significantly (p< 0.05) reduced. The animals treated with 25.0 or 37.5 mg/kg streptozotocin developed mild to moderate hyperglycaemia, but their body weight gain was similar to controls. The relationships between streptozotocin dose and metabolic responses (plasma glucose, glycosylated haemoglobin, urinary glucose, food intake, etc.) were clearly demonstrated. Systolic blood pressure rose with progressing age in both controls and streptozotocin-treated rats, irrespective of dosage or metabolic response. This new rat model of Type 2 diabetes associated with persistent hypertension may be useful in studying these combined effects on small and large vessels.

We designed the present study to clarify whether the development of nephropathy was accelerated by a combination of hypertension and non-insulin-dependent diabetes. Spontaneously hypertensive rats with non-insulin-dependent diabetes induced by neonatal streptozotocin treatment (25.0–75.0 mg/kg) were separated into severely or mildly diabetic groups according to their non-fasting plasma glucose levels at 12 weeks of age and the findings were compared with the data on a control group treated with citrate buffer alone. The natural courses of urinary excretion rate of total protein, the molecular composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis with laser desitometer and N-acetyl-β-D-glucosaminidase were measured in the three groups from 12 weeks until 36 weeks of age. Total urinary protein in the control group decreased with age (p<0.05), while in the mildly diabetic group changes were nil; in the severely diabetic group, however, the excretion rates of total urinary protein and high molecular weight protein consistently and progressively increased with age (p<0.05). The low molecular weight protein continuously decreased with age in the mildly diabetic and control groups (p<0.05), while in the severely diabetic group there was no decrease after 28 weeks of age. The urinary N-acetyl-β-D-glucosaminidase markedly increased (p<0.05) in the severely diabetic group throughout the period compared with findings in the control group, but drastically decreased (p<0.05) in the mildly diabetic group with age. There were significant correlations between the mean glycosylated haemoglobin levels and all the urinary parameters measured (p<0.05). These observations suggest that development of nephropathy is accelerated by the glycaemic level in hypertensive rats. This new model should be appropriate for studying the combined effects of hypertension and diabetes mellitus on the kidney.