Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Implants of rabbit neonatal pancreas, encased in 'Nucleopore' chambers (0.4 micrometer) reversed streptozotocin-induced diabetes in the rat. Blood-glucose, plasma-insulin, and oral glucose-tolerance test returned to normal. An isolated, perfused, streptozotocin-treated pancreas removed from a diabetic animal did not secrete insulin and removal of implants after 6 weeks from six animals caused all animals to die in hyperglycaemia within 8 days. This shows that the implant did not lead to the re-establishment of endogenous pancreatic function. Implanted diced neonatal pancreas in three chambers removed after 6 weeks secreted glucagon, insulin, and pancreatic polypeptide in vitro. No rejection reactions were seen. Rabbit neonatal pancreatic implants may thus be feasible therapy in insulin-requiring diabetic patients. Implants of other non-syngeneic endocrine cells--i.e., pituitary, thyroid, and ovary--may be useful in other hypoendocrine syndromes.
 ...
PMID:Reversal of streptozotocin-induced diabetes in rats by intraperitoneal implantation of encapsulated neonatal rabbit pancreatic tissue. 7 54

Pancreatic islet-cell antibodies (ICA) are important markers for two subtypes of insulin-dependent diabetes mellitus and stain the entire islet in the standard immunofluorescence test. This could indicate either a mixture of antibodies each directed against one cell type, or a population of antibodies reacting with a single antigen common to the endocrine pancreas. In the present experiments such a common antigen was demonstrated visually by application of animal antisera raised to each of the 4 pancreatic hormones, together with ICA-positive sera in a four-layer double immunofluorescent technique employing green and red anti-Ig conjugates. Double exposure photographs demonstrated that the patients' sera reacted equally with the different endocrine cells. The ICA antigen did not cross-react with gastric glucagon- or somatostatin-cells. By contrast, human antibodies against glucagon-cells (GCA) or somatostatin-cells (SCA) reacted with discrete antigens specific to each cell type and in 50% of cases the antibodies also stained the respective endocrine cells in the gastrointestinal tract. These refined discriminatory properties of human autoantibodies may lead to a better understanding of the intracellular membrane systems in these important endocrine organs.
 ...
PMID:Islet-cell antibodies (ICA) in diabetes mellitus (evidence of an autoantigen common to all cells in the islet of Langerhans). 8 9

A 53-year-old white woman developed diabetes mellitus, migratory erythema, and anemia, clinical features suggesting the presence of a "glucagonoma." Ten years earlier, after laparotomy and pancreatic biopsy, she had been told that she had an inoperable pancreatic carcinoma. Review of that biopsy together with current hormonal assay now confirms the diagnosis of glucagonoma. The recurrent peptic ulcer in this patient despite high levels of glucagon, a gastric inhibitory agent, is noted but not explained. An enhanced amylase-creatinine clearance ratio supports the notion that glucagon increases the clearances of amylase.
 ...
PMID:Glucagonoma, chronic recurrent peptic ulcer disease, and enhanced amylase-creatinine clearance ratio. Report of a case with review of the literature. 9 10

Alrestatin, a lens aldose reductase inhibitor, decreased i.v. arginine-induced glucagon levels and augmented arginine-stimulated insulin release in the ether anesthetized rat. Alrestatin may then be useful in the treatment of diabetes mellitus, due to its actions on insulin and glucagon, and its capacity to delay the onset of sugar-induced cataracts in the rat.
 ...
PMID:Effect of alrestatin on arginine-induced secretion of glucagon and insulin in the rat. 9 19

Radioimmunological method was applied to the study of glucagon content in patients with diabetes mellitus of different severity and duration of the disease. Glucagon level on fasting stomach in patients with diabetes at the state of compensation failed to differ from that in healthy persons. But in decomensated disease with the ketoacidosis phenomena there was a sharp elevation of glucagon content with restoration to the normal after the compensation was reached. In patients with diabetes mellitus complicated by diabetic retinopathy blood glucagon content failed to correlate with the incidence of retinopathy. However, there was a direct relationship between the incidence of retinopathy and the duration of the disease. In adipose diabetic patients glucagon content was elevated, but this rise was insignificant in comparison with healthy persons.
 ...
PMID:[Nature of changes in glucagon secretion in diabetes mellitus]. 9 60

Streptozotocin-induced diabetes in the rat can be reversed by the transplantation of isogenic islets of Langerhans from neonatal donors. We studied the morphology of intraportally transplanted islets with the aid of the immunoperoxidase staining technique to identify insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-containing cells at 24 hours, 48 hours, 1 week, 2 weeks, 4 weeks, 39 weeks, and 65 weeks after transplant. Embolized pancreatic tissue, composed of approximately 80% acini and 20% islets, is initially distributed throughout the liver mainly to terminal branches of the portal system. Endothelialization and organization occur rapidly with the smaller fragments and within the first 4 weeks for larger thrombi. Exocrine pancreatic elements largely disappear as islet cells move into the hepatic lobules from the portal spaces. At 65 weeks after transplant, all islet cell types can be identified within large complex islet structures. The results of this study establish the survival and continued function of all known rat pancreatic islet cell types long after transplantation and support the theory that islet transplantation may represent the most physiologic replacement of hormonal deficiencies in the diabetic recipient.
 ...
PMID:The fate of intraportally transplanted islets in diabetic rats. A morphologic and immunohistochemical study. 9 48

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

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

For more than half a century the management of hyperglycemia in diabetes mellitus has included rigid diets and intermittent subcutaneous insulin administration. These methods have been totally unsuccessful in restoring glucose homeostasis to normal in most diabetic patients. This review focuses on techniques that offer promise as alternatives or adjuncts to the current modalities of treatment. Specific areas discussed include pancreatic transplantation, islet cell transplantation, artificial beta cell devices, and the glucagon-suppressing agent somatostatin. Although many of these show promise for the future, a cure for the metabolic abnormalities of diabetes is not imminent.
 ...
PMID:Treatment of diabetes mellitus: the future. 10 34

This study reviews the pathogenic hormonal abnormalities (insulin deficiency and stress hormone excess) in diabetic ketoacidosis. The data both supporting and negating a primary role for insulin deficiency in the pathogenesis of diabetic ketoacidosis are examined. Evidence implicating excess stress hormone secretion as a necessary event in the development of severe metabolic decompensation is discussed. The data suggest that diabetic ketoacidosis may be prevented by correcting either the relative deficiency of insulin or the excess secreation of one or a combination of the stress hormones. Studies supporting a primary role for insulin deficiency in the pathogenesis of diabetic ketoacidosis include the beneficial therapeutic response to insulin administration in ketoacidosis, development of ketoacidosis; and (3) stress hormone excess is necessary for fulminant ketoacidosis to be manifested.s following insulin withdrawal from diabetic man and animals, and hypoglycemic and hypoketonemic effects of insulin. Studies negating a primary role for insulin deficiency in ketoacidosis include the "normal" plasma insulin concentration in the majority of ketoacidotic cases, delayed onset of ketoacidosis after insulin withdrawal from diabetic man, and lack of hypolipolytic and hypoketonemic effect of insulin without prior stress hormone adipocyte and hepatocyte stimulation. Evidence that stress hormones (glucagon, catecholamines, cortisol, and growth hormone) contribute to the metabolic decompensation of ketoacidosis includes: (1) in all cases of ketoacidosis, at least one stress hormone is always elevated; (2) pharmacologic blockade of each of the stress hormones reduces the rate and/or frequency of metabolic decompensation in diabetic man; (3) removal of the pituitary and/or the adrenal gland in diabetic animals completely prevents the development of ketoacidosis after insulin withdrawal; and (4) administration of each of the four stress hormones under appropriate conditions induces metabolic decompensation in diabetic man with "normal" circulating levels of plasma insulin concentration. From these studies, the following conclusions are supported: (1) absolute insulin deficiency is an unusual cause of ketoacidosis; (2) the presence of relative insulin deficiency is necessary for the development of ketoacidosis; and (3) stress hormone excess is necessary for fulminant ketoacidosis to be manifested.
Diabetes Care
PMID:Pathogenesis of diabetic ketoacidosis: a reappraisal. 11 31


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