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)

Cholecystokinin (CCK) is a known stimulus for the release of insulin and other islet hormones. To localize islet cell CCK binding sites, we measured the uptake of 125I-CCK by the isolated, perfused rat pancreas. Light microscope autoradiographs revealed uptake of label over both the endocrine islets of Langerhans and the exocrine acini. This uptake of 125I-CCK was saturable, as it decreased markedly when a large excess of unlabeled CCK8 was included in the perfusion solution. To define which cells in the islets bound CCK, electron microscope autoradiographs were prepared. The majority of silver grains in islets were localized over beta cells (69%), although saturable uptake was also observed over alpha (12%) and other islet cells. When grain densities were analyzed (grains/micron 2), the highest density was observed over islet blood vessel cells. In contrast to islet blood vessels, there was no localization of 125I-CCK over acinar blood vessels. This study supports the concept, therefore, that there is a direct regulation of islet endocrine cells by CCK, and also raises the possibility that CCK influences islet hormone release via an indirect effect on the islet vascular endothelium.
Diabetes 1985 Apr
PMID:Localization of saturable CCK binding sites in rat pancreatic islets by light and electron microscope autoradiography. 298 85

Insulin acutely inhibits the catecholamine-stimulated rise in cAMP levels in fat, liver, and muscle primarily through stimulation of the enzyme cAMP phosphodiesterase (PDE). Adipocytes from rat epidydimal fat pads were exposed to insulin and fractionated by centrifugation. Whereas the cytosolic fraction contained a low-affinity cAMP PDE that was unaffected by insulin, the activity of a high-affinity enzyme residing in a particulate fraction was increased by insulin. This enzyme activity could be solubilized with nonionic detergent and chromatographed on ion exchange followed by chromatofocusing. The resulting enzyme preparation was subjected to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Silver staining revealed a single band with a molecular weight of 60,000. This apparent molecular weight was verified by calculation of the hydrodynamic properties of the enzyme. Evaluation of its kinetic properties indicated that the enzyme activity residing in this solubilized 60,000-Mr protein exhibited lower affinity than the membrane-bound enzyme but was still specific for cAMP. Activation of this enzyme may be one of the primary mechanisms by which insulin counteracts the effects of adenylate cyclase-stimulating hormones.
Diabetes 1986 Jun
PMID:Purification of putative insulin-sensitive cAMP phosphodiesterase or its catalytic domain from rat adipocytes. 301 73

A case of sulindac-induced toxic epidermal necrolysis (TEN) is described; the etiology, symptoms, and treatment of TEN are reviewed; and sulindac's pharmacokinetic characteristics and other adverse effects are discussed. A 62-year-old black woman was given a prescription for sulindac 150 mg twice daily to relieve pain associated with degenerative joint disease. She also had a nine-year history of type II diabetes mellitus that was being managed with tolbutamide 500 mg once daily. After two weeks of sulindac therapy she developed a rash that spread over her entire body. Sulindac therapy was discontinued, and one day later the patient was admitted to the hospital with a temperature of 104.6 degrees F, conjunctivitis, and an erythematous macular rash over 60% of her body. Initially, therapy included prednisone 160 mg orally every day, applications of silver sulfadiazine cream four times daily for two days, and methylcellulose 0.5% ophthalmic solution (two drops four times daily) for the conjunctivitis. She also received intravenous hydration. By the fifth hospital day the patient's skin lesions and conjunctivitis had improved to the point that the prednisone dosage was tapered to 120 mg, then to 80 mg, and then to nothing over the following three days. Her diabetes was managed by short-term treatment with NPH insulin; however, before discharge, tolbutamide therapy was reinstituted, and insulin was discontinued. At follow-up four weeks after discharge, the patient's skin was largely clear. TEN has multiple etiologies, but the basic mechanism of injury is believed to be an immunological reaction directed at the basal cell layer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sulindac-induced toxic epidermal necrolysis. 323 97

Because there is evidence for vagal autonomic neuropathy as the cause of diabetic gastroparesis, we hypothesized that this disorder should be associated with morphologic abnormalities of the abdominal vagus nerve or gastric myenteric plexus, or both. We studied the smooth muscle and myenteric plexus of the stomach in 18 nondiabetic controls and 16 patients with long-standing diabetes. Five of the diabetics had gastroparesis and 11 did not. We utilized conventional histology and Smith's silver technique for visualizing the myenteric plexus. Neurons within the myenteric plexus were quantified in sections stained with each technique. The abdominal vagus nerves from 5 diabetics (2 with gastroparesis) and 12 nondiabetic controls were stained with hematoxylin and eosin, Gomori trichrome, luxol-fast blue, and Holmes' silver stains. There were no abnormalities in the numbers or appearance of neurons or axons in the myenteric plexus of the stomach of diabetics, with or without gastroparesis. Also absent were abnormalities of the smooth muscle or vagus nerve. Thus, no morphologic abnormalities of the gastric wall or abdominal vagus were identified in diabetic gastroparesis.
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PMID:There are no morphologic abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis. 334 91

The internalization and intracellular distribution of 125I-insulin-like growth factor II (125I-IGF II) in mouse isolated pancreatic acini was studied by electron microscope autoradiography. 125I-IGF II was rapidly internalized; after 30 min over 70% of silver grains derived from the bound hormone were localized over the interior of the cells. The grain distribution from 125I-IGF II differed significantly from both a random grain distribution and that derived from bound 125I-insulin. The majority of intracellular 125I-IGF II grains were over the endoplasmic reticulum and Golgi; the Golgi showed the highest density of intracellular grains. Pretreatment of acini with 10 nM cholecystokinin octapeptide (CCK 8) reduced both the amount of acinar-associated IGF II and the density of intracellular 125I-IGF II grains. Moreover, CCK 8 altered the relative distribution of grains from 125I-IGF II between organelles. These studies indicate, therefore, that 125I-IGF II is internalized by pancreatic acini, and that this internalization is regulated by CCK 8.
Diabetes Res Clin Pract 1986 May
PMID:Autoradiographic analysis of 125I-insulin-like growth factor II internalization into pancreatic acini. 352 49

Post-mortem samples of parotid gland were obtained from 15 patients with a history of diabetes mellitus for a minimum of 5 years, and from 15 age- and sex-matched controls. The tissue was studied by direct immunofluorescence for abnormal binding of selected serum proteins, including IgG, IgM, IgA, C3, fibrinogen, polyvalent immunoglobulin and albumin, to acinar and ductal basement membranes of the gland. Thickness of these basement membranes was also assessed using a calibrated magnifier on uniformly enlarged photomicrographs of the tissue which had been stained by the chromotrope silver methenamine method to highlight basement membranes. Results of this investigation revealed parotid gland basement membrane abnormalities in all diabetic subjects as indicated by the binding of IgG, albumin and polyvalent immunoglobulins to ductal and acinar basement membranes. These basement membranes were uniformly negative in control subjects for the binding of all serum proteins tested. Binding of IgA was also noted in 7 of 15 experimental subjects, with 6 of these representing Type I diabetics. Basement membrane measurements revealed no difference in thickness between diabetic and non-diabetic subjects. Variations in parotid diabetic basement membranes evidenced in this study further substantiate the idea that membranopathy in this disease is systemic in nature.
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PMID:Parotid gland basement membrane variation in diabetes mellitus. 392 79

Light touch and low-frequency vibration sense deteriorate during the development of diabetic neuropathy. As Meissner corpuscles are mechanoreceptors that respond to these sensations, this study explored the structural changes of neurites in Meissner corpuscles of diabetic mice C57BL/Ks(db/db). We evaluated silver impregnated neurites from forepaw digital pads from 46 diabetic and 46 nondiabetic female mice which ranged in age from 2.5 to 17 months. Light microscopically, neurites from diabetic mice were less coarse, less tortuous, and exhibited decreased varicosity and decreased corpuscle size compared with those from nondiabetic mice. Number of corpuscles per area and neurite intraepidermal continuations showed a statistically significant decrease with age and with diabetes. Projected area and width of neurites, measured within a fixed interval on camera lucida tracings, showed both a statistically significant increase with age and a decrease with diabetes. Neurite complexity was unchanged between diabetics and nondiabetics. These findings suggest that axonal dwindling, a characteristic of peripheral nerves in diabetes, extends to the receptors and occurs throughout the lifespan of the mouse.
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PMID:Age-related changes of neurites in Meissner corpuscles of diabetic mice. 394 57

The reduction of high serum LH levels toward or to normal in diabetic women in the menopausal range recorded during the first year of treatment with a synthetic progestin, 17-alpha-ethynyl-19-nortestosterone acetate, 3-cyclopentylenol ether (quingestanol acetate), was maintained during the second and third years of daily ingestion of this steroid. Normal LH and normal or high FSH levels prior to therapy were not affected. Other endocrine indices, including serum PBI and T4, plasma 11(OH) corticosteroids, serum growth hormone titers, insulin responses to oral glucose, and urinary excretion of 17-ketosteroids, Porter-Silber chromogens, and 11-desoxycortisol metabolites, estrogens, and creatinine remained relatively unchanged during quingestanol therapy. At the 36th month of treatment, a small increase in fasting blood glucose levels with greater hypoglycemia after oral carbohydrate was noted, but this probably reflected the natural history of treated diabetes mellitus. The decrease in urinary steroid responses to partial blockade of adrenal 11-beta hydroxylase by metyrapone observed in the 12th month of quingestanol therapy was not evident at the end of 24 and 36 months of treatment. Quingestanol therapy was associated with maintenance of the increase in serum sodium from low-normal to mid-normal concentrations noted during the first year of treatment. Serum chloride increases were less frequent. Other serum electrolytes, solutes, proteins and other nitrogenous constituents, lipids, and enzymes and formed blood elements generally fluctuated within the pre-therapy ranges. Body weight, blood pressure, pulse rate, electrocardiograms, and perception of vibrations were about the same prior to and at the completion of the three-year course of therapy. The steroid was well tolerated.
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PMID:Prolonged progestin (quingestanol) therapy of menopausal diabetic women. 446 59

Foetal mouse brain cells were cultured as described previously [Sotelo, Gibbs, Gajdusek, Toh & Wurth (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 653-657] without added insulin and without foetal calf serum after 12 days in culture. Examination by phase-contrast microscopy showed that these modifications did not appear to affect growth and development of the cells adversely. Silver impregnation of the cultures and indirect immunofluorescence following reaction with tetanus toxin showed that a high proportion of the cells resembled neurones. Analysis of concentrated culture medium by radioimmunoassay and high-pressure liquid chromatography (h.p.l.c.) revealed that the cells produced two main forms of immunoreactive insulin which differed from authentic pancreatic insulin in retention time. Immunoreactive somatostatin was also produced in culture and this was resolved into at least three forms by h.p.l.c. Immunoreactive insulin was also extracted from whole rat brain by using two published procedures. The method of Havrankova, Schmechel, Roth & Brownstein [Proc. Natl. Acad. Sci. U.S.A. (1978) 75, 5737-5741] consistently gave greater yields of insulin than did that of Eng & Yalow [Diabetes (1980) 29, 105-109] and the concentration was about three times that of plasma. The extracted insulin was further characterized by h.p.l.c. in each case and was found to behave like authentic pancreatic insulin. The production of insulin and somatostatin by foetal mouse brain cells in culture suggests that they may be a useful model system for studies of neuropeptide biosynthesis.
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PMID:Immunoreactive insulin from mouse brain cells in culture and whole rat brain. 614 53

In the islets of rat pancreas, steroid diabetes induced by triamcinolon-acetonid led to glycogen infiltration of B cells. Ultracytochemically, glycogen was detected within 24 hours after glucocorticoid administration using the periodic acid-silver proteinate method according to Maxwell (1978). Glycogen was primarily located in the cytoplasm of granulated B cells but could also be detected in the halo of the secretory granules of these cells. The amount of glycogen increased during the course of the 5 day experiment. The A, D, and PP cells were free of glycogen.
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PMID:Ultrastructural distribution of glycogen in pancreatic islets of steroid diabetic rats. 639 90


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