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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Langerhans islets were isolated from the exocrine pancreata of Wistar rats by the improved collagenase-digestion method. The isolated islets were preserved in a tissue culture medium for seven days. Transplantation of these preserved islets into the portal vein of streptozotocin-induced diabetic rats resulted in a significant reduction of hyperglycemia, polyuria and glucosuria, and a restoration of weight gain. It was found that these effects could be maintained for 16 weeks. In order to normalize the K-values and plasma insulin levels, at least 600 islets had to be transplanted into each diabetic rat.
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PMID:Transplantation of preserved pancreatic islets into the portal vein of rats. 9 59

The intraportal injection of 350 to 1,000 isolated islets into streptozotocin-diabetic rats immediately normalized (approximately 24 hours) fasting plasma glucose and insulin levels. Polyuria, polydipsia, and hyperglucagonemia disappeared more gradually over a 2-to-12-week period--the time required for normalization varying with the severity of the diabetes and the number of islets transplanted. In long-term islet-transplanted rats (greater than five months), the hepatic insulin and glucagon reserves averaged 50 per cent and 25 per cent, respectively, of the corresponding normal pancreatic hormone content. Glucagon was increased slightly in the pancreas of streptozotocin-diabetic rats and decreased considerably in transplanted animals. However, total pancreatic glucagon (i.e. pancreatic and hepatic reserves) in transplanted animals was the same as the pancreatic content of normal control rats, indicating the presence of feedback control mechanism(s) in the regulation of pancreatic glucagon reserves. Long-term transplanted islets demonstrated well-granulated A-, B-, and D-cell movement out of the vascular space and the formation of narrow intercellular spaces and junctional complexes with surrounding hepatocytes.
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PMID:Metabolic and morphologic studies in intraportal-islet-transplanted rats. 13 76

Sufficient numbers of pancreatic islets transplanted into the splenic pulp of streptozotocin-induced diabetic rats can result in complete reversal of hyperglycemia, glycosuria, and polyuria while promoting weight gain. These changes are constant for at least 3 months. Animals transplanted in this way, however, fail to exhibit a normal biphasic insulin response during an intravenous glucose tolerance test. This lack of biphasic response is in marked contrast to that observed in portal-vein--transplanted animals. Basal serum insulin in intrasplenic-transplanted animals is twice that observed in normal animals and portal-vein--transplanted animals which have received the same number of islet isografts. Direct injection of islets into the splenic pulp does not insure that subsequently all islets will remain in the splenic pulp, and, in fact, subsequent splenectomy suggests that in some cases a majority of transplanted tissue lodges in other organs--most likely, the liver.
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PMID:Intrasplenic islet isografts. 14 12

The present study was undertaken to clarify the mechanism of the diabetogenic activity of streptozotocin. Experiments were conducted to determine the resistance of animals to the diabetogenic action of streptozotocin; to follow the time course of irreversible beta-cell damage, and to determine the influence on streptozotocin action of certain compounds. Streptozotocin, a broad spectrum antibiotic, with antitumoral properties, was shown to be diabetogenic in rats and mice, but not in cats, rabbits, or guinea pigs. Intravenous or intraperitoneal administration of 65 mg/kg body weight of streptozotocin to male Wistar rats evoked a tri-phasic blood sugar response. It induced an initial hyperglycemic peak with no apparent change in plasma insulin concentrations, followed by profound hypoglycemia caused by liberation of large amounts of insulin from the pancreas. Forty-eight hours after injection, the animals were completely diabetic. Light- and electron-microscopic exadminations during the first forty-eight hours after the injection of streptozotocin showed pyknosis, degranulation and marked degeneration of the beta-cells. 1egenerative and necrotic changes were also seen in a few alpha-cells. These streptozotocin-induced diabetic rats revealed polydipsia, polyuria, polyphagia and glucosuria, and decreased body weight. Blood sugar, plasma FFA and insulin concentrations were examined after oral administration of glucose (OGTT: 3g/kg). Blood sugar and plasma FFA were significantly elevated but plasma insulin concentrations were markedly decreased, so insulin treatments were most effective in these animals. It has been reported that nicotinamide prevents the diabetogenic activity of streptozotocin and the deformity action of 6-aminonicotinamide and 3-acetylpridine. Pre-treatment with picolinamide, methyl-nicotinamide, and nicotinohydroxamic acid also blocked its diabetogenic action, but nicotinic acid, mannoheptulose and glucose were ineffective. N-nitrosodimethylamin and ethyl-N-nitrosomethylcarbamate were devoid of diabetogenicity. It seems that streptozotocin interfers with NAD formation in the beta-cell. Functioning pancreatic islets cell tumors were observed on the rats both at 407 days after streptozotocin administration and at 473 days after streptozotocin administration with nicotinamide (500 mg/kg, i.p.).
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PMID:[Studies on the mechanism of the diabetogenic activity of streptozotocin and on the ability of compounds to block the diabetogenic activity of streptozotocin (author's transl)]. 16 68

In a boy aged 42 months, small stature, retarded psychomotor development, dry skin, excessive thirst, polyuria, cryptorchidism, and rickets were signs of multihormonal disturbances. Contrary to the clinical manifestations, laboratory investigations showed normal or raised levels of hormones (hGH, insulin, T3RU, T4, TSH, PTH). The cAMP level in the plasma was low and its urinary excretion was reduced. After administration of hGH, adrenaline, T3, T4, pitressin, vitamin D3 and aminophylline there was no rise in the cAMP concentration in plasma and urine. In the light of these results it may be assumed that deficient function of the adenyl cyclase system led to development of a clinical syndrome of tissue insensitivity to multiple hormonal factors in this case.
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PMID:Cyclic 3',5'-adenosine monophosphate (cAMP) in a 42-month-old child with clinical evidence of multiple hormonal disturbances. 22 75

A new, spontaneously diabetic syndrome has been recognized in nonobese outbred Wistar rats of both sexes. The age at detection of first glycosuria has varied from 48 to 120 days, with a mean of 67 days. Eighteen rats have been studied, 14 untreated and four during and after cessation of insulin treatment. The affected animals have demonstrated a spectrum of severity, with hyperglycemia (252-732 mg./dl.), hypoinsulinemia (0-1 ng./ml.), and hyperketonemia. The severely ketotic rats, with total blood ketone body levels between 6 and 13 mM, showed rapid loss in weight and dehydration over one to six days. The moderately ketotic (1-5 mM) declined gradually in weight over 15 days, with marked polyuria and glycosuria. The stable rats, with ketonemia less than 1 mM, sustained their weights, polyuria, and glycosuria for longer than 40 days. A relative or absolute increase in plasma immunoreactive glucagon and elevated levels of free fatty acids and branched-chain amino acids were observed in relation to the severity of the syndrome. Intraperitoneal arginine or tolbutamide elicited no insulin response, but the glucagon response to arginine was exaggerated. Pancreatic insulin content was normal or moderately decreased. Light-microscopic examination of pancreases of ketotic animals at the end stage of the disease showed islets to be very small and rare, consisting virtually of non-beta cells. In stable and earlier ketotic rats, the islets were small, with reduction in beta-cell number and a striking inflammatory cell infiltration. Surviving beta cells showed variable degranulation. This model of spontaneous diabetes in nonobese rats displays insulin deficiency, glucagon excess, and ketosis, with a dramatic inflammatory lesion during active beta-cell destruction.
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PMID:The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. 32 72

Spontaneous diabetes mellitus was diagnosed in six of 126, 13-lined ground squirrels, Citellus tridecemlineatus. Serum glucose values were significantly higher in the diabetic ground squirrels than in the non-diabetic ground squirrels, while serum insulin values of fasted diabetic squirrels were significantly lower than fasted nondiabetic ground squirrels. In addition, the classic diabetic signs of poly-dipsia, polyuria, glycosuria, ketonuria, polyphasia, and weight loss were present. The proportion of islet tissue to total pancreatic area in diabetic ground squirrels was less than 25% of that in the nondiabetic ground squirrels. Both the number and size of the islets of Langerhans in diabetic ground squirrels were less than those in nondiabetic ground squirrels.
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PMID:Diabetes mellitus in the 13-lined ground squirrel (Citellus tridecemlineatus). 33 78

Reversal of insulinopenia, hyperglycemia, glycosuria, and polyuria associated with severe alloxan diabetes in the rat was accomplished by syngeneic transplantation of whole late-gestation fetal rat pancreata. Intravenous glucose tolerance test (GTT) revealed an improved yet still abnormal glucose and insulin response in reversed recipients reconstituted with as few as two pancreata from fetal donors. Eight fetal donors were sufficient to return glucose and insulin response following GTT to normal. Seventy to eighty percent fewer donors were required when the pancreata were transplanted in their entirely as opposed to transplantation of pancreata subjected to prior enzymatic and mechanical dissociation. The facility and simplicity of the whole fetal pancreas implantation technique makes it an appealing model for further study of islet growth and differentiation at the transplant site and of its effect on the metabolic state of the recipient.
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PMID:Syngeneic transplantation of the fetal rat pancreas IV. Dissociated versus whole organ implantation. 36 9

An acute onset with polyuria and polydipsia is the pattern of onset for something approaching 90 per cent of child diabetics. Their management, then, must include insulin and diet together with education of the parents in how to use these measures.
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PMID:General management of the diabetic child. 88 Jan 44

We have recorded clues to the clinical recognition of chronic insulin overdosage in 101 pediatric patients with diabetes mellitus, identified predisposing circumstances, and reconsidered the traditional strategy of slow reduction in insulin dose. Overtreatment occurred in 70%, overall, and in 90% of those referred for instability; mean overdose was 38% of the readjusted dose. The most common findings were frank hypoglycemic episodes, polyuria/nocturia/enuresis despite increasing insulin dosage, excessive appetite, hepatomegaly, weight gain, headaches, exercise intolerance, marked variation in glucosuria, mood swings, and frequence bouts of rapidly developing ketoacidosis. Overtreatment usually developed because of attempts to achieve metabolic control using glucosuria as principal criterion. One fourth of those observed became overtreated during periods of emotional turmoil when need for increased insulin to counter stress-induced hyperglycemia and ketosis led to chronic increase in dosage. Persistent glucosuria/ketonuria and exacerbation of hypoglycemic symptoms were more frequent with slow than with rapid reduction in insulin dosage.
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PMID:Chronic overtreatment with insulin in children and adolescents. 88 3


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