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

The streptozotocin diabetic rat (STZ-DM) has been the best animal model for the study of insulin-deficient diabetes. A spontaneous diabetic BB Wistar Rat (SDR) has now been evaluated as a model for insulin-dependent diabetes that more closely reflects this disease in humans. The authors assessed the ability of insulin to stimulate the Vmax of a low Km cAMP phosphodiesterase (PDE) in adipose tissue of control, streptozotocin diabetic (STZ-DM) rats, and spontaneous diabetic BB rats (SDR). In addition, the authors examined the effect of streptozotocin on the nondiabetic littermates of the SDR animal, the NDR rat. Insulin stimulated Vmax of low Km cAMP PDE in control rat adipose tissue by 20% at 5 minutes. Insulin also stimulated Vmax of both SDR and NDR by 50% at 5 minutes. In contrast to control and both subgroups of the BB rat (SDR and NDR), insulin stimulated adipose tissue from STZ-DM less than 10% at 5 minutes. NDR animals rendered diabetic with streptozotocin were more responsive to insulin. The data demonstrate some similarities and differences between streptozotocin-induced diabetes and spontaneous diabetes in the BB rat. Reduced responsiveness to insulin appears to be more a part characteristic of streptozotocin diabetes than diabetes in the BB rat. The absence of significant insulin resistance in the spontaneous diabetic BB rat also is more consistent with the pathophysiological mechanisms usually seen both in other insulin-dependent diabetic rat models and insulin-dependent diabetes in man. However, both animal models of diabetes, ie, STZ-DM and BB, like man, respond to insulin therapy.
 ...
PMID:Studies of insulin resistance in the streptozotocin diabetic and BB rat: activation of low Km cAMP phosphodiesterase by insulin. 254 91

Three weekly intraperitoneal injections of complete Freund's adjuvant (CFA) and, one day later, 25 mg/kg of STZ have been reported to cause a gradual onset of autoimmune diabetes. We have previously reported that the onset of diabetes in this model occurs too rapidly to be due to a specific immune reaction and that other compounds that activate macrophages also potentiate low-dose STZ in rats. We have proposed that mediators released from activated macrophages may enhance the cytotoxic effect of STZ. In the present study, we have observed that intraperitoneal injections of silica, a macrophage toxin, markedly decrease the incidence and severity of diabetes induced with CFA and low-dose STZ.
Diabetes Res 1989 Jun
PMID:Silica prevents the induction of diabetes with complete Freund's adjuvant and low-dose streptozotocin in rats. 255 26

Untreated streptozocin-induced diabetic (STZ-D) rats have previously been shown to have significantly increased hypothalamic concentrations of neuropeptide Y (NPY), a regulatory peptide that powerfully stimulates eating and drinking and inhibits secretion of several pituitary hormones when injected centrally. Tissue NPY concentrations have been measured by radioimmunoassay in selected hypothalamic regions microdissected from fresh, unfixed brain slices to localize diabetes-associated NPY changes precisely within the hypothalamus. Significant (35-200%) increases in NPY concentrations (P less than .01 vs. matched nondiabetic controls) were found in specific hypothalamic regions between 3 and 14 wk after induction of STZ-D. These regions included the paraventricular and ventromedial nuclei and lateral hypothalamic area, major appetite-regulating areas that are sensitive to the hyperphagic and polydipsic actions of NPY. Increased NPYergic activity in these areas may, at least partly, drive the increased eating and drinking characteristic of STZ-D. NPY concentrations were also increased in the arcuate nucleus and medial preoptic area. Because both of these regions are important in modulating pituitary hormone secretion, local NPY increases may be involved in the impaired secretion of luteinizing hormone, thyroid-stimulating hormone, growth hormone, and prolactin known to occur in STZ-D. Our finding of NPY increases in specific hypothalamic nuclei associated with functional changes found in STZ-D suggests that this peptide may have a role in the altered metabolic and neuroendocrine regulation of the syndrome.
Diabetes 1989 Mar
PMID:Increased neuropeptide Y concentrations in specific hypothalamic regions of streptozocin-induced diabetic rats. 256 12

Eighteen timed-pregnant Syrian golden hamsters were injected subcutaneously with streptozotocin (STZ, 60 mg/kg bw) early on gestational day 10. The response varied widely, and based on changes in blood glucose levels during gestational days 11 to 15, the hamsters were categorized into four groups: 1) no change; 2) mild diabetes (200-250 mg/dl), which reverted; 3) moderate diabetes (greater than 300 mg/dl), which reverted; and 4) moderate to severe diabetes (300-500 mg/dl), which was sustained. Two hours before sacrifice, a 25 mg tablet of bromodeoxyuridine (BrdU) was implanted subcutaneously into each experimental hamster and into 17 control pregnant hamsters that had not received STZ. BrdU-labelling was demonstrated immunochemically in the pancreatic islet cells. In control hamsters, the mean labelling index (LI) of the islet cells was 0.07% and did not exceed 0.2% in any hamster. Following injection of STZ, islet cell LI's remained low (0.13%) if the blood glucose levels were not altered by the diabetogenic drug. However, LI's were increased in islet cells of hamsters which showed a mild to moderate diabetes which rapidly reverted; the highest LI's (5% +/- 2.1) occurred in four hamsters that were killed 2 days after receiving STZ. The LI's were moderately increased (1.4% +/- 0.42) in two hamsters with moderate diabetes killed 2 days after STZ, but LI's were low (0.12% +/- 0.04) in six hamsters with moderate to severe diabetes killed 3, 4, and 5 days after STZ. Reversion of hyperglycemia to normoglycemia correlated closely with increased DNA synthesis in the islet cells of the pregnant hamsters. These observations strongly suggest that following mild cytotoxic injury induced by STZ, the B cells regenerated and insulin production was restored sufficiently to maintain normoglycemia.
 ...
PMID:Correlations between blood glucose levels and bromodeoxyuridine labelling indices of pancreatic islet cells following streptozotocin administration to pregnant Syrian golden hamsters. 256 82

Right atria from rats rendered diabetic by injection of streptozocin (STZ-D) for 8-10 wk are supersensitive to the negative chronotropic effects of muscarinic agonists but have decreased levels of muscarinic receptors and acetylcholinesterase activity. Insulin treatment completely prevents the development of these changes. The proportion of atrial muscarinic receptors displaying high-affinity agonist binding is lower in STZ-D rats; however, the sensitivity of high-affinity agonist binding to regulation by a guanine nucleotide (5'-guanylylimidodiphosphate) is greater in atria from diabetic rats. Again, insulin treatment eliminates these differences. These findings indicate that alterations in atrial muscarinic systems in STZ-D rats are a consequence of the elaboration of the diabetic state and suggest that an alteration of functional muscarinic receptor-G protein coupling contributes to the altered physiological responsiveness of the heart in diabetes.
Diabetes 1989 Dec
PMID:Insulin prevention of altered muscarinic receptor-G protein coupling in diabetic rat atria. 257 55

Various parameters were used in observing the process of wound healing in rats with streptozotocin-induced diabetes (STZ diabetes). Sections stained according to the Hematoxylin-Eosin, Van-Gieson, and Azan methods were used in observing histological changes. At the same time, wound strength during the healing was measured as a parameter for evaluating the healing process. In addition, changes in leukocytes, plasma fibrinogen, activated factor XIII (aXIII), collagen content of the incised wound, and metabolic changes were determined. Results 1. Histological studies showed that, in STZ diabetes, the inflammatory response was minimal and occurred later than in normal cases. In the incised wound, cellular infiltration of polymorpho-nuclear leukocytes and fibrin nets accumulated poorly. The fibrin net was coarse and fragile. Furthermore, epithelialization of the wound was late: it did not occur until 5 days after the operation. In cases of STZ diabetes, patterns of hyperplasia and fibroblast arrangements were abnormal. Collagen regeneration and proliferation processes were remarkably retarded. 2. In normal, wound strength increased from the 5 postoperative day. After 10 days had passed, it increased remarkably until, after 30 days, it had returned to the preoperative level. In STZ diabetes, however, no increase in wound strength occurred for the first 14 days after the operation. There after strength increased slowly; but, 40 days after the operation, 80% of the preoperative level still had not been reached. 3. Changes in leukocytes were much later occurring in STZ diabetes than in normal. Recovery took longer than in normal. 4. In STZ diabetes, increases in plasma fibrinogen and decreases of the aXIII factor were slower than in normal. The a XIII factor decreased remarkably, and recovery was slow. 5. In terms of collagen content in the wound incision, in STZ diabetes, tropocollagen increase occurred later than in normal. But, from the 5 to the 14 postoperative days, its level was higher than that in normal. Maturation-process collagen and mature collagen increased still more slowly. In normal, mature collagen had reached preoperative level 20 days after the operation, in STZ diabetes, 80% of preoperative level still had not been reached 30 days after the operation. 6. These studies showed that the following factors hinder wound healing in cases of diabetes mellitus: minimal inflammatory response, incomplete formation of the fibrin nets, retardation of epithelialization, retarded action of plasma fibrinogen and the a XIII factor, reduced fibroblast activity, and slow increase in collagen content.
 ...
PMID:[Experimental studies of skin wound healing process by first intention in streptozotocin-induced diabetes mellitus rats]. 263 77

The concentrations of acetylcholine (ACh) as a parasympathetic marker and norepinephrine (NE) as a sympathetic marker were investigated in the hearts of rats 2, 4, and 8 wk after the induction of diabetes by an injection of streptozocin (STZ; 65 mg/kg i.v.). ACh and NE were measured by high-performance liquid chromatography with electrochemical detection. Diabetic rats showed low body weight and heart weight at 2, 4, and 8 wk and higher heart-to-body weight ratio and bradycardia at 8 wk, almost all of which were normalized after insulin treatment. Myocardial ACh and NE concentrations in the diabetic rats at 2 and 4 wk were not significantly different from those in age-matched control rats. However, ACh and NE concentrations in the diabetic rats at 8 wk significantly increased compared with the control rats. Diabetic rats at 8 wk also had increased myocardial choline concentration and choline acetyltransferase activity and decreased acetylcholinesterase activity. Insulin treatment normalized all of these changes in the diabetic rats. Thus, in STZ-induced diabetes (STZ-D), the concentrations of both cholinergic and noradrenergic neurotransmitters in the myocardium increased. The results of this study confirm a previously reported increase in sympathetic activity to the heart and also indicate that there is an increase in the synthesis and a decrease in the metabolism of ACh in STZ-D and that adequate insulin treatment normalizes these changes.
Diabetes 1989 Feb
PMID:Altered acetylcholine and norepinephrine concentrations in diabetic rat hearts. Role of parasympathetic nervous system in diabetic cardiomyopathy. 264 43

To investigate the role of the mediobasal hypothalamus (MBH) in diabetic gonadal axis disorders, the MBHs of adult male streptozocin-induced diabetic (STZ-D) rats were examined after incubation in basal conditions or in K+-enriched medium and compared with those of controls. Diabetes lasted 1 mo. Both luteinizing-hormone-releasing hormone (LHRH) release and MBH morphology were studied. After incubation in basal conditions, the LHRH release was unchanged. By light microscopy, the dilated-axon cross sections were more numerous (P less than .01) in the basal arcuate nucleus and in the median eminence. By electron microscopy, the ratio of exocytoses to neurosecretory granules observed in the median eminence axon cross sections was smaller (P less than .05). The total LHRH immunoreactivity, the number of labeled axons, and the amount of positive material in the axons were reduced (P less than .05). After incubation in K+-enriched medium, the LHRH release was markedly reduced (P less than .01). The number and area of dilated-axon cross sections, possibly because of the relation between exocytosis and physiological dilation, were less augmented (P less than .01). Whereas the number of exocytoses and the ratio of exocytoses to neurosecretory granules were not decreased, the total LHRH immunoreactivity and the number of labeled axons were reduced (P less than .05). The releasable LHRH pool therefore seems to be exhausted in control MBH because of long-term stimulation and reduced in the MBH of STZ-D rats because of diabetes. In conclusion, STZ-D causes functional and anatomical MBH lesions that should be pathogenetically relevant for the disorders of the gonadal axis documented in this animal model.
Diabetes 1989 Apr
PMID:Functional and morphological changes in mediobasal hypothalamus of streptozocin-induced diabetic rats. In vitro study of LHRH release. 264 54

Previous studies have shown that adenosine, by activation of purinergic A2-receptors, stimulates glucagon secretion and increases vascular flow rate in isolated perfused pancreases from nondiabetic rats. Because alpha-cell function and blood flow control are known to be disturbed in diabetes, we investigated whether adenosine was still effective in streptozocin-induced diabetic (STZ-D) rats. Our experiments were performed on isolated perfused rat pancreases. Whereas, in normal rats, adenosine (1.65 microM) induced a 200% increase in glucagon output and a 25% rise in the pancreatic vascular flow rate, in rats diabetic for 5-6 wk, this nucleoside was ineffective on glucagon secretion, and its vasodilatory effect was strongly reduced. Long-term in vivo insulin treatment that reversed high glycemia levels was able to restore in large part both adenosine effects. In contrast, a short-term in vitro pretreatment with insulin was unable to restore the nucleoside effects. We conclude that STZ-D suppresses the stimulatory effect of adenosine on alpha-cells and strongly reduces its vasodilator properties; these abnormalities may be corrected in large part by long-term insulin treatment with normalization of glycemia.
Diabetes 1989 Oct
PMID:Diabetes and impaired response of glucagon cells and vascular bed to adenosine in rat pancreas. 267 58

Earlier studies revealed a general amelioration of diabetes-induced alterations in the rat following chronic oral vanadyl treatment. Recently, some streptozotocin-diabetic animals treated similarly were observed to remain euglycemic after withdrawal from vanadyl. In the present study, the diabetic profile of these animals (STZ-T) was investigated. After 3 weeks of treatment with vanadyl followed by 13 weeks of withdrawal, plasma concentrations of glucose, insulin, lipids, and thyroid hormones in the STZ-T animals were returned to control levels. Myocardial dysfunction and increased glycerol output from adipose tissue in untreated-diabetic (STZ) rats were also found to be normalized in the STZ-T group. Furthermore, there was no evidence of cataracts in these animals compared with age-matched STZ rats. These findings indicate that short-term oral treatment of diabetic rats with vanadyl induces beneficial changes that persist following withdrawal of the treatment. The results of these studies may suggest a possible new treatment protocol that could be incorporated into the management of diabetes.
 ...
PMID:Sustained prevention of myocardial and metabolic abnormalities in diabetic rats following withdrawal from oral vanadyl treatment. 267 9


<< Previous 1 2 3 4 5 6 7 8 9 10