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)

Longitudinal studies of the rhesus monkey reveal a syndrome of diabetes mellitus in those that become middle-aged and obese. The sequence of events in the development of the disease progresses from normoinsulinemia with normoglycemia through stages of hyperinsulinemia followed by below normal insulin levels with hyperglycemia and glycosuria. We believe the rhesus to be an excellent nonhuman primate model for maturity-onset diabetes in humans.
 ...
PMID:The course of development of glucose intolerance in the monkey (Macaca mulatta). 10 70

Changes in glucagon, growth hormone (GH), cortisol, renin and aldosterone accompanying the metabolic disturbances and dehydration of severe diabetic ketoacidosis were studied over a 24 h period in eight patients treated with a constant intravenous insulin infusion. Mean steady state plasma-free insulin levels achieved were 28.6--49 mu/1 in patients receiving 2 u/h but a satisfactory rate of fall of glucose was not always obtained until the infusion dose was increased to 4 u/h or more. The total insulin dose administered was positively correlated with the level of plasma glucagon and cortisol on admission. During insulin infusion, both glucagon and cortisol fell but the rate of fall was not related to dose or plasma level of free insulin achieved. In six of eight patients studied increments in plasma GH above admission levels were observed during insulin treatment. Admission values of both plasma renin activity and plasma aldosterone were raised. The renin levels were highest in newly diagnosed diabetics, and two patients with long-established diabetes showed only small increments despite profound dehydration. Plasma renin activity, but not plasma aldosterone correlated with the fluid and sodium retention over the initial 24 h treatment period, but not with potassium requirements. The urinary excretion rates of the small molecular weight proteins GH and insulin, were considerably elevated over the treatment and convalescent periods.
 ...
PMID:Hormonal responses during treatment of acute diabetic ketoacidosis with constant insulin infusions. 10 71

This study investigates the effects of insulin antibody binding on free insulin levels measured in patients with acute diabetic ketoacidosis receiving insulin by constant infusion. In spite of antibody binding ranging from 10 to 90 per cent of the total circulating insulin, the steady state concentrations of free insulin were similar to those observed in individuals on identical infusion rates but without insulin-binding antibodies. However, the levels of free insulin in two patients were substantially lower than expected for the rate of insulin infusion, even though levels of bound insulin were not greatly elevated. An infusion rate of at least 4 U. per hour produced satisfactory rate of fall of plasma glucose, whereas lower dose regimens (2 U. per hour)--producing steady state free insulin concentrations ranging from 28 to 49 mU. per liter in different subjects--were unreliable in controlling the metabolic abnormalities of diabetic ketoacidosis.
Diabetes 1978 Dec
PMID:Antibody binding of insulin in diabetic ketoacidosis. 10 56

This study is a description of a patient who exhibited diabetic ketosis associated with an alkalosis rather than acidosis and a review of eight previously reported cases. Precipitating factors for this syndrome are severe vomiting with loss of hydrogen, potassium, and chloride ions, and dehydration. The ingestion of alkali may also result in this mixed acid-base disturbance. Treatment consists primarily of replacement of potassium and chloride. All reported patients had received large doses of insulin for initial therapy; however, limited insulin (20 U) therapy in this patient almost completely reversed the metabolic abnormality with 12 hours.
Diabetes Care
PMID:Mixed acid-base abnormalities in diabetes. 10 96

Chromium (III) has recently been shown to be an essential trace mineral in rats, being required for normal function of insulin in controlling glucose metabolism. Chromium is transported in the body bound to transferrin, where it binds competitively with iron. Hemochromatosis is an iron storage disease in humans characterized by highly saturated transferrin levels and sometimes by diabetes. We postulated that the diabetes may be due to exclusion of chromium by iron at metabolic binding sites. 51Cr(III) was administered i.v. to 5 normal males, 6 patients with hemochromatosis prior to therapeutic removal of iron, and 5 patients with varying levels of iron loading. The retention of 51Cr was measured with a whole-body counter for 8 mo and blood levels were measured for 40--80 days. Analysis of the whole-body retention curves revealed 3 exponential components with T1/2s of .56 days, 12.7 days, and 192 days; the blood curves had 4 components with T1/2s of 13 min; 6.3 hr, 1.9 days, and 8.3 days. The T1/2s were not significantly different between the normals and patients. The coefficients of these components however, were significantly lower for the long T1/2 components in the iron-loaded patients, demonstrating reduced retention of 51Cr as postulated. Whether this reduced retention of chromium is causally related to diabetes in hemochromatosis and whether abnormal chromium metabolism is involved in endogenous diabetes, thus, becomes an important question for future study.
 ...
PMID:Reduced chromium retention in patients with hemochromatosis, a possible basis of hemochromatotic diabetes. 10 24

Experiments were conducted on rabbits. A study was made of the effect of administration of maninyl (glybenclamide) into the stomach in a dose of 10 mg/kg of body weight for 7 days on the blood glucose level, insulin and zinc content in the pancreatic islands, and on the "dithizone" diabetes development. Maninyl administration was accompanied by a significant glycemia reduction. The amount of deposited insulin and zinc determined histochemically was sharply reduced up to complete disappearance from the majority of beta-cells. "Dithizone" diabetes was not reproducible in animals given maninyl preliminarily: the required condition for induction of this affection was formation of zinc dithizonate in beta-cells.
 ...
PMID:[Antidiabetogenic activity of maninyl]. 10 51

Transplantation of adult rat pancreatic islet tissue as a free graft requires the separation of islet from exocrine tissue to avoid host injury or graft destruction by digestive enzymes. The poor yield from islet isolation techniques currently necessitates the use of multiple donors to ameliorate diabetes in a single recipient. DL-ethionine (DLE) is an agent selectively toxic to the exocrine pancreas. We examined the effect of DLE administration on pancreatic digestive enzyme content and islet mass in adult Lewis rats and the ability of such pancreatic tissue dispersed by collagenase digestion without specific islet isolation to ameliorate diabetes when transplanted to the portal vein of syngeneic rats with streptozotocin induced diabetes. Rats fed normal chow supplemented with 0.5% DLE for 14-20 days showed a logarithmic loss of pancreatic mass. Total pancreatic amylase content declined to 0.3 + 0.1 mg, less than 3% of control values (14.3 +/- 1.0 mg). Total insulin content in DLE treated rats was 87 +/- 8 microg, not significantly different from control rats (101 +/- 7 microg). Histological examination confirmed the selective atrophy of exocrine tissue in DLE treated rats. Fresh pancreatic tissue prepared from a single DLE treated donor ameliorated diabetes 75% of the time when transplanted to one or two recipients and 65% of the time when divided between three of four recipients. Tissue prepared from a single DLE treated donor and stored for 24-48 hours ameliorated diabetes 91% of the time when divided between one or two recipients. Only four of 31 diabetic rats transplanted with fresh pancreatic tissue from untreated adult donors became normoglycemic. Pretreatment of adult rats with DLE induces selective exocrine atrophy, permits dispersed pancreatic tissue from a single donor to ameliorate experimental diabetes in up to four recipients, and allows tissue to be preserved by culture for up to 48 hours without specific islet isolation.
 ...
PMID:DL-ethionine treatment of adult pancreatic donors. Amelioration of diabetes in multiple recipients withe tissue from a single donor. 10 81

Implantable artificial capillary units containing approximately 1,200 allogeneic rat islets, or approximately 3,000 xenogeneic rabbit or human islets as an implantable artificial endocrine pancreas (IAEP) were implanted in streptozotocin-induced (55 mg/kg) diabetic rats. A total of 26 rats received IAEP containing allogeneic islets. Twenty were short term experiments which lasted for 12-24 h. Four recipients survived between 1-3 days and the remaining two for 4 and 11 days respectively. Five diabetic rats received IAEP containing xenogeneic islets. The four recipients of IAEP containing rabbit islets survived up to 4 days while the recipient of IAEP containing human islets survived for 8 days. Following implantation, a decrease of plasma glucose from the initial value of 500 mg/dl to normoglycaemia and a corresponding increase in circulating levels of insulin up to 100 muU/ml were observed in the recipient animals. Furthermore the IAEPs were shown to produce a near normal plasma glucose and insulin response to an intravenous glucose tolerance test. These findings suggest the feasibility of achieving amelioration of diabetes with allogeneic or xenogeneic pancreatic islets implanted as an artificial endocrine pancreas unit in the experimental animals which has the potential of future clinical application in man.
 ...
PMID:Implantable artificial capillary unit for pancreatic islet allograft and xenograft. 10 55

Calcium distribution in B cells of the isolated perfused rat pancreas was examined by the pyroantimonate precipitation technique in relation to the insulin secretory pattern of the perfused pancreas in response to 3 mM or 20 mM D-glucose or 20 mM D-glucose in calcium-depleted ethylene glycol tetra-acetic acid (EGTA) medium. Perfusion fixation after various time intervals from 3 to 30 min allowed appropriate relation to secretory phases. Qualitative and quantitative evaluation of the precipitation patterns revealed a significant increase in cell membrane associated percipitates after 3--5 min of perfusion with 20 mM glucose compared with the results after perfusion with 3 mM glucose. After 10--30 min of perfusion with 20 mM glucose there was an additional significant increase in precipitates located in the cytoplasm and the halos of the secretory granules. Perfusion with 20 mM glucose in calcium-deprived EGTA medium strongly reduced the number of precipitates within the B cells. The results suggest that cell membrane associated calcium may be involved in exocytosis, and by its sudden increase may trigger the first phase of insulin secretion. The calcium stores in the cytoplasm and the granules may be of importance for long-term regulation of insulin release.
Diabetes 1979 Jun
PMID:Ultracytochemical calcium distribution in B cells in relation to biphasic glucose-stimulated insulin release by the perfused rat pancreas. 10 39

Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not inhibited by N-ethylmaleimide. The soluble fraction also degraded glucagon and B chain but not growth hormone or myoglobin. It was inhibited by incubation with the patient's nonketotic sera, normal sera, or Trasylol. Glutathione-insulin-transhydrogenase (GIT) activity was 66% of normal. The biopsy of adipose tissue at remission showed a normal level of insulin- and glucagon-degrading activity. The activity was eluted from Sephadex G200 as a single peak and had properties consistent with those of the insulin-specific protease (ISP). The increased degrading activity present during insulin resistance had properties not shared with ISP, suggesting the presence of an uncharacterized protease.
Diabetes 1979 Jul
PMID:Insulin resistance caused by massive degradation of subcutaneous insulin. 10 40


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