Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that renal prokallikrein synthesis is reduced in streptozotocin (STZ)-diabetic rats. Plasma renin activity is also reduced in diabetic rats. To investigate the molecular mechanisms underlying these changes, we examined the effects of diabetes and insulin treatment on renal kallikrein and renal renin mRNA levels and the activities of these enzymes. Rats made diabetic by STZ were either treated with 1.5 to 1.75 U PZI insulin daily to maintain moderate hyperglycemia (plasma glucose 200 to 300 mg/dl, D + I) or left untreated to produce severe hyperglycemia (plasma glucose greater than 400 mg/dl, D). Control (C) rats were also studied. After three weeks, renal kallikrein mRNA was reduced 50% in D rats. A proportional reduction in immunoreactive kallikrein was also observed (37.8 +/- 2.5 vs. 55.8 +/- 6.8 ng/mg protein, D vs. C, P less than 0.001). Kallikrein mRNA and immunoreactive kallikrein levels in D + I rats were not different from C rats. Renin mRNA level was also markedly reduced in D rats, compared to C rats. This was associated with reduced plasma renin concentration (4.5 +/- 0.2 vs. 10.5 +/- 1.6 ng Ang I/ml/hr, D vs. C, P less than 0.01). However, renal renin concentration was unchanged (0.84 +/- 0.17 vs. 0.84 +/- 1.3 micrograms Ang I/mg protein/hr, D vs. C). In D + I rats, renin mRNA level and plasma renin concentration were not different from C levels. However, renal renin concentration was increased (1.49 +/- 0.27 micrograms Ang I/mg protein/hr) compared to C rats (P less than 0.05). beta-actin mRNA levels were unchanged in either diabetic rat group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of diabetes and insulin on expression of kallikrein and renin genes in the kidney. 151 1

Lente insulins can be mixed in any ratio at any time. Regular plus NPH insulins seem to be the preferred mixture of rapid- and intermediate-acting insulins because the effect of the combined insulins is the same as that of regular and NPH insulin injected separately. Mixing regular with lente insulins is more complex and needs further study. However, at the present time, if regular and lente insulins are going to be mixed, they should be either mixed and injected immediately, or they should be left to interact for up to 24 hours, in which case the resultant mixture does not have as rapid an action as the immediately injected mixture. Combinations of regular and protamine zinc insulins are rare and complicated by the fact that the resultant product is based upon the ratios of regular to PZI. Generally speaking, protamine zinc insulin is rarely used in humans. It is used by some veterinarians, especially to treat cats with diabetes. The Table summarizes information concerning the mixing of various insulins.
Diabetes Educ
PMID:Mixing insulins in 1990. 220 72

Diabetes mellitus causes a cardiomyopathy in human subjects, independent of atherosclerotic coronary artery disease. Ventricular papillary muscle function studies in chronically diabetic rats and rabbits have shown diminished contractility and a prolonged duration of contraction. In rats there was complete reversibility of these changes with insulin therapy. However, the effects of insulin on the myocardial mechanics of diabetic rabbits have not been studied. Therefore, rabbits diabetic for 3-4 mo (after alloxan injection) were treated with PZI insulin for 3-4 mo, and the mechanical performance of their right ventricular papillary muscles was compared with that of untreated diabetic animals and age-matched controls. Insulin therapy normalized serum glucose concentration. All abnormalities in papillary muscle function were completely reversed in insulin-treated animals. Norepinephrine (NE) dose responses were also evaluated in muscles from all groups. There were no differences in the positive inotropic effects of NE between groups. However, the data suggested, in diabetic animals a blunted response of peak relaxation rate to NE; this abnormality was reversed in muscles from treated animals. These findings indicate that previous work on diabetic rats can be extended to diabetic rabbits and suggest that chronic insulin therapy completely reverses the contractile alterations in hearts from these diabetic animals.
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PMID:Reversibility of diabetic cardiomyopathy with insulin in rabbits. 351 May 67

In diabetic rats transplanted with fetal pancreata we measured the activities of six important enzymes to assess the return of liver metabolism to normal. Comparison was made among the responses of transplanted rats with and without renal-portal vein shunts and of those not transplanted and injected with insulin in varying doses. Insulin supply was not limited since three or four fetal pancreata were first grown in normal rats before transfer into the diabetic animals. Transplantation normalized blood and urine glucose and the rate of disappearance of intravenous glucose. Glucokinase and pyruvate kinase activities in liver rose toward normal at 7 days after transplantation and reached normal levels at 30 and 90 days. The response of the other four enzymes, glucose-6-phosphate dehydrogenase, citric lyase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase, was more rapidly restored to normal at 7 days and remained normal at 30 and 90 days. No difference was observed in the enzyme activities of transplanted-shunted rats to nonshunted animals. Glucokinase activity was restored to normal after 1 wk of daily injections of 1 U of PZI; pyruvate kinase restoration required 3 U/day. Glucose-6-phosphate dehydrogenase and citric lyase required 2 U/day to be restored to normal; 3 U daily resulted in temporary supernormal activities. The gluconeogenic enzymes, fructose-1,6-bisphosphatase and glucose-6-phosphatase, were only partially suppressed toward normal by insulin even with 3 U daily for 3 wk. These findings indicate that pancreas transplantation is a more effective regulator of liver metabolism in diabetes than insulin injections.
Diabetes 1983 Aug
PMID:Normalization of six key hepatic enzymes after fetal pancreas transplantation in diabetic rats. 630 89

Peripheral neuropathic alterations associated with diabetes and its treatment with insulin were studied in alloxan-induced diabetic rats. Treatment regimens included daily injections of Protamine Zinc Insulin (PZ), daily injections of Ultralente Insulin and subcutaneously implanted osmotic minipump delivered insulin. Non-diabetic and untreated diabetic groups served as controls. Two separate but similar studies were run, one lasting 4 weeks and the other 8 weeks. Conduction velocities performed on both sensory and motor nerves revealed no statistically significant differences among groups. Anatomical analysis of teased fibers from tibial nerves showed a significant number of fibers with ovoids, consistent with Wallerian-type axonal degeneration, only in the treated diabetic groups. Degeneration was especially severe in the PZI-treated group. Metabolic studies were performed using incorporation of radioactive isotopes ([3H]fucose, [14C]leucine) into myelin proteins of sciatic nerves. The ratio of [3H]fucose/[14C]leucine for the PZI-treated group was significantly decreased when compared to the control groups in both the 4 and 8 week study whereas the minipump-treated group showed no statistically significant difference from the control group in either study. Similar decreases in this ratio have been seen in conditions of peripheral nerve degeneration. It is concluded that daily injections of PZI insulin result in significant nerve degeneration in the alloxan diabetic rat, while continuous levels of insulin delivered by osmotic minipumps result in less degeneration.
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PMID:Degenerative neuropathy in insulin-treated diabetic rats. 635 99

Diabetes appears to cause a cardiomyopathy independent of atherosclerotic coronary artery disease and hypertension. Left ventricular papillary muscle function studies in rats made severely diabetic with streptozotocin have shown a slowing of relaxation and a depression of shortening velocity. However, the effects of insulin therapy on the myocardial mechanics of diabetic rats have not been studied. Therefore, rats diabetic for 6-10 weeks were treated with PZI insulin for 2, 6, 10, or 28 days and the mechanical performance of their left ventricular papillary muscles was compared to that of untreated diabetics and age-matched controls; cardiac contractile protein enzymatic activity was also measured. Neither 2 nor 6 days of therapy had any effects on the depressed cardiac muscle performance of diabetic animals, although plasma glucose concentration was restored to normal. By 10 days of therapy, recovery of mechanical performance was nearly complete, and by 28 days of therapy, complete reversal of the altered myocardial mechanics was observed. Crystalline insulin added to the bath (9 mU/ml) had no effect on myocardial mechanics in either diabetics or controls. A gradual recovery of actomyosin and myosin ATPase activity in the hearts of insulin-treated diabetic animals was also found, complementing the mechanical studies. In addition to demonstrating a gradual but complete reversibility of the abnormalities in papillary muscle function in diabetic rats (although control of hyperglycemia was less than ideal), this study confirms that this model of a cardiomyopathy is not a result of streptozotocin-induced cardiac toxicity. Additional data are provided indicating that depressed thyroid hormone levels in diabetic rats are not responsible for the mechanical changes observed.
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PMID:Reversibility of diabetic cardiomyopathy with insulin in rats. 703 May 13

The efficacy of a new protamine zinc formulation based on recombinant insulin (PZIR) was compared with a veterinary-approved beef/pork-source insulin (PZI VET, Idexx Pharmaceuticals) that has been shown to significantly decrease blood glucose in cats with diabetes mellitus (DM). After being examined and weighed and having blood collected for determination of serum fructosamine concentrations, 50 cats with DM and stable glycemic control on PZI VET were switched to PZIR for 30 days at the same dose rate and interval. There was only one reported episode of hypoglycemia, and the cat was withdrawn from the study. In the 47 cats completing the study, there were no significant differences in body weight or serum fructosamine concentrations at days 15 or 30 compared with day 0. The results of this study indicate that PZIR provides glycemic control that is comparable to that of PZI VET when used at the same dose and dosing interval.
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PMID:Preliminary study of protamine zinc recombinant insulin for the treatment of diabetes mellitus in cats. 1974 45