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)

In the islets of the rat pancreas, steroid diabetes induced by triamcinolon-acetonid leads to degranulation of the B cells and glycogen infiltration. The glycogen cannot be satisfactorily detected using methods like the chromic acid technique according to Bauer, staining with Best's carmine, or the usually applied periodic acid-Schiff (PAS) reaction. Glycogen detection is improved, however, when lead tetraacetate is used in place of periodic acid as oxidizing agent. When combining the carbohydrate detection method with the peroxidase--antiperoxidase (PAP) method used for immunocytochemical detection of the various pancreatic islet hormones, paraffin sections reveal that glycogen is primarily localized in granulated B cells; the degranulated B cells also contain glycogen, though in smaller amounts. In contrast, the islet cells containing somatostatin, glucagon and pancreatic polypeptide are nearly free of glycogen.
 ...
PMID:Glycogen in pancreatic islets of steroid diabetic rats. Carbohydrate histochemical detection and localization using an immunocytochemical technique. 703 7

Until the discovery of insulin by Banting and Best in 1922, diabetes had a high mortality rate. Since then regular administration of the drug has brought it under control. Nevertheless it is not an ideal drug, in that it has to be injected and because of the incidence of insulin resistance. There is, therefore, a need for alternative forms of treatment and in recent years interest has centred on the possibilities of vanadium salts.
 ...
PMID:Vanadium salts and the future treatment of diabetes. 768 98

A long-term investigation of bone mineral metabolism in a newly developed strain, the WBN/Kob rat, which spontaneously develops diabetes, possibly due in part to hemosiderin deposition, was conducted. WBN/Kob rats used in this study developed diabetes after 9 months of age. Bone mass peaked at 6 months or 8 months of age, and femoral breaking strength was maximal at 8 months of age, declining rapidly after the development of diabetes. In contrast, both the bone mass and the mechanical strength increased up to 14 months of age in controls. The serum osteocalcin (BGP) levels were lower at 4 months of age and serum 1.25(OH)2D levels were significantly lower throughout the study in WBN/Kob rats than in controls. These results suggest that abnormal bone and mineral metabolism is present in WBN/Kob rats before the onset of diabetes, and that bone strength and BMD decrease simultaneously with the development of diabetes. This strain can serve as a useful model, not only of hemosiderosis and diabetes, but also of osteopenia.
 ...
PMID:WBN/Kob rat: a new model of spontaneous diabetes, osteopenia and systemic hemosiderin deposition. 771 21

The human insulin in replacement therapy has a hexameric structure. Hexamerization of the insulin molecule facilitates biosynthesis and beta-cell storage of insulin, but is unnecessary for biologic activity and appears to contribute to delayed absorption of exogenous insulin from the subcutis. Insulin analogues with reduced self-association that are produced through recombinant DNA techniques have been shown to have in vivo activity comparable to that of human insulin and absorption kinetics characterized by higher and more constant rates of disappearance from the subcutaneous injection site. In preliminary studies in patients receiving insulin therapy, monomeric insulin analogues have been found to provide glycemic control in the postprandial period that is at least equivalent to that of human insulin. Findings in these studies suggest that the use of such analogues may provide meal-related insulin effects closer to those observed in the physiologic state by limiting excessive postprandial glucose excursions and decreasing the risk of late hypoglycemia. Banting and Best revolutionized diabetes therapy 70 years ago with the extraction of insulin from animal pancreas glands (J Lab Clin Med 7:464-472, 1922). Since that time, many refinements of the therapeutic properties of pharmaceutical preparations of the hormone have been introduced. Until recently, however, such advances have been limited to improvements in insulin purity, insulin species, and adjustment of the composition of the vehicle with respect to auxiliary substances and other additives. With the advent of recombinant DNA techniques, it has become possible to optimize the insulin molecule itself for purposes of replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
J Diabetes Complications
PMID:Design of insulin analogues for meal-related therapy. 851 52

The discovery of insulin by Banting and Best in 1992 is the subject of many papers and one authoritative book (Bliss M. The Discovery of Insulin. Chicago: University of Chicago Press, 1982. See also Bliss M. Rewriting medical history: Charles Best and the Banting and Best myth. J Med Hist 1993; 48: 253-274.). This paper charts the introduction of insulin in England and examines its effects on medical practice. Before 1922 there were few effective drugs and only one (thyroid extract) which had to be taken continuously. Insulin was radically different; it restored weight and vigour and allowed survival in diabetic coma and after surgery but was potentially dangerous because of the possibility of hypoglycaemia, had to be given by injection, and the dose varied with the amount of food and exercise. The immediate questions to be answered after the supply of insulin was assured were how could such a powerful drug be kept out of the hands of ignorant people (a phrase used by The Times), who would administer it, and who would supervise the treatment? Within a year further problems were identified. Should the aims of treatment be the same as those in the starvation era? Could the diet be liberalized? How much biochemical monitoring was necessary? I set the scene by describing how, from Minkowski's announcement (1889) that pancreatectomy caused severe diabetes, most clinicians and physiologists believed that the pancreas (and specifically the islets of Langerhans) produced an internal secretion which controlled carbohydrate metabolism. After Murray's (1891) demonstration that myxoedema could be cured by thyroid extract, it was assumed that diabetes would soon yield in the same way. Yet by the beginning of the First World War most experts were pessimistic about isolating the hypothetical internal secretion and had pinned their hopes on starvation treatment. In the decade before the introduction of insulin the management of diabetes was grim; patients were kept in hospital for weeks or months, while their calorie intake and glucose excretion was meticulously recorded. They were in the wards of physicians with a strong interest in biochemistry whose forte was analysing urine not looking after patients. When the Medical Research Council set up a multicentre trial of insulin in late 1922 they enrolled the physician biochemists who produced the early publications and became the experts. The narrow views and innate conservatism of these doctors with the inflexibility of the system in (London) teaching hospitals meant that insulin treatment became a straightjacket for many patients.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:A force of magical activity: the introduction of insulin treatment in Britain 1922-1926. 854 34

When a medical problem is intensively studied by many teams in the world, it is frequent to see the solution found simultaneously in different countries. However that was not exactly the case concerning the extraction of a potent insulin able to cure Diabetes Mellitus. It seems necessary, seventy five years later, when passions are quenched, to reconsider the chronology of the history and put Paolesco but also Collip at the right places much before Banting and Best to whom, by a curious misinterpretation of facts, was attributed the priority of this fundamental discovery.
 ...
PMID:[The discovery of insulin]. 870 82

A nude mouse xenotransplantation model was established for human thyroid carcinomas of different histological types. Best results of serial passages were obtained in anaplastic cancers. The models allowed investigations under in vivo conditions. Hormonal influences were tested, and imaging procedures were possible. In most aggressive anaplastic carcinoma cell lines, growth inhibition of cytostatic drugs, cytokines and nutritional effects were investigated.
Exp Clin Endocrinol Diabetes 1996
PMID:Xenotransplantation of human thyroid carcinomas in athymic nude mice. 898 29

When a medical problem is studied intensively by several investigators in the world, a solution may sometimes be found simultaneously in different countries. Seventy-five years after the discovery of insulin, the chronology of this event can be reconsidered objectively and the role of each of the protagonists evaluated. The stubbornness of Banting and Best, the technical abilities of Collip and the active support of Macleod were determinant in the use of insulin for the treatment of diabetic patients. Moreover, in the long line of experimentalists and physicians, Lancereaux and Paulesco also deserve special mention.
Diabetes Metab 1997 Feb
PMID:[The 75th anniversary of the discovery of insulin]. 910 93

Nonenzymatic glycosylation (glycation) of proteins, often referred to as the Maillard reaction, has been proposed to play a role in age and diabetes-related processes by forming protein and DNA adducts and cross-links. These cross-links may contribute to erectile dysfunction by scavenging nitric oxide, which is needed for erection. As the basis for a possible role of the advanced Maillard reaction in age-related erectile dysfunction, we investigated the presence of the specific advanced glycation endproduct (AGE) pentosidine in penile corpus cavernosum tissue and penile tunica albuginea tissue as a function of age. A total of 23 penile tissue specimens were obtained at autopsy, from which 19 samples of tunica albuginea and 21 samples of corpus cavernosum were derived. In addition, 13 penile corporal and tunical specimens were procured at the time of insertion of a penile prosthesis, from which 12 tunica albugineal specimens and 10 samples of corpus cavernosum were derived. Collagen was extracted with acetic acid and pepsin digestion, and the final insoluble collagen product was acid-hydrolyzed with 6 N HCL for 24 h at 110 degrees C. Pentosidine was quantified by high-performance liquid chromatography using a reverse-phase column. The level of pentosidine (expressed in picomoles per milligram of insoluble collagen) was found to increase with age in cadaver as well as living penile corporal and tunical albugineal tissues. Best-fit analysis revealed an exponential increase in both types of cadaver penile tissue, with regression equations of y = 15.29 x 10(9.9e-3x), R2 = 0.79, being obtained in the tunica and y = 13.2 x 10(7.63e-3x), R2 = 0.56, in the corpora. These correspond to 6- and 4-fold increases in pentosidine levels from puberty to the age of 100 years (P < 0.05), respectively. Mean pentosidine levels were higher in the tunica than in the corpora. Comparison of pentosidine levels in the tunica versus the corpora revealed a weakly linear correlation (y = 24.88 + 1.08x, R2 = 0.32). Levels in the tunical and corporal specimens from the living human specimens fell with the predicted confidence intervals of the cadaveric tissue. Tunical specimens from patients who underwent repair or revision of a previously inserted penile prosthesis had very low levels of pentosidine. The exponential age-related increase in pentosidine observed in both types of penile tissue suggests an impairment of collagen turnover, which could be related to the advanced glycation reaction in aging. It is not known whether pentosidine itself is directly associated with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification. Formation of advanced Maillard reaction products, which is greatly accelerated in aging, diabetes, and uremia, could contribute to erectile dysfunction in these syndromes.
 ...
PMID:Age-related increase in an advanced glycation end product in penile tissue. 911 57

The most celebrated medical discovery of this century is comprised of two distinct stages: (1) that of fundamental research, i.e. the experimental demonstration of the presence in the pancreas of an antidiabetic hormone done by Paulescu and published on 31 August 1921 in the Archives Internationales de Physiologie; and (2) the clinical application of the discovery of insulin in the treatment of diabetes in man, the stage completed in 1922 by the Canadian group comprised of Collip, Macleod, Banting and Best.
 ...
PMID:Insulin, the molecule of the century. 912 75


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