UMLS:C0011854 - FACTA Search

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Query: UMLS:C0011854 (type 1 diabetes)
20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, in vitro B-cell models are described, which may be applicable for studying the reported B-cell desensitization produced by hyperglycemia in IDDM and NIDDM. Using a programmable perifusion/perfusion system, insulin secretion from perifused islets was measured at 10-30-min intervals for 24-50 h. After 3-4 h continuous glucose (11 mM), a new phase of insulin release occurs in which secretion declines to, and remains at, approximately 25% maximal release. Results were similar when using: perifused islets embedded in Cytodex 3, or Bio-Gel P-2, 100-200 mesh; batchincubated islets with hourly changes of medium; and the isolated pancreas perfused for 8 h. Three different media, Hana HB 104 (fortified, fully defined medium), RPMI-1640 + 10% FBS, and perfusion bufferalbumin, were used. Despite reduced secretion to continuous glucose, each system responded vigorously to an acute stimulation with glucose-forskolin. Decreased secretion was primarily caused by decreased secretagogue efficiency (reduced fractional secretion). Prolonged stimulation with glucose or glucose-IBMX produced a similar waning of secretion regardless of the amount of insulin released. It is concluded that the third phase of insulin secretion may represent a secret-agogue-induced, signal desensitization of the B-cell, rather than exhaustion of a B-cell compartment of stored insulin.
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PMID:The third phase of in vitro insulin secretion. Evidence for glucose insensitivity. 351 47

It has been widely reported that dysfunctions of pancreatic A-cell occur in diabetics. Since these pancreatic A-cell dysfunctions are not normalized by conventional insulin injection treatment, they were thought to be a primary defect of diabetes mellitus. Recently it was found that paradoxic glucagon secretion to oral glucose and excessive glucagon response to i.v. arginine could be perfectly normalized if strict blood glucose regulations were achieved with appropriate insulin treatment. However, there has been no report on the perfect normalization of glucagon secretion in response to insulin-induced hypoglycemia in diabetics. In this report, to elucidate the precise significance of A-cell function in hypoglycemia in diabetics, the effect of long-term strict glycemic regulations and the importance of intact autonomic nerve function on hypoglycemia-induced glucagon secretion were studied. In experiments on hypoglycemia-induced glucagon secretion in diabetics, 0.2 to 0.3 U/kg of regular insulin injection were usually employed to overcome the hyperglycemia and insulin resistance. However, hyperinsulinemia has been demonstrated to suppress A-cell function in experiments using the euglycemic clamp technique. Therefore, the effect of plasma insulin concentrations after insulin injections was first studied in 7 healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. In this experiment with 0.3 U/kg of insulin, the rate of fall in glycemia and the nadir of blood glucose were made similar to that with 0.1 U/kg of insulin by using glucose clamp technique with artificial endocrine pancreas. The plasma glucagon response after 0.3 U/kg of insulin was significantly suppressed as compared to that after 0.1 U/kg of insulin. From these experiments, it was concluded that not only hypoglycemic stimuli but also plasma insulin concentrations are important factors for demonstrating significant glucagon secretion in response to insulin-induced hypoglycemia. Second, the effects of strict glycemic control and autonomic nerve function on hypoglycemia-induced glucagon secretion were studied. Regular insulin at a dose of 0.1 U/kg was injected in an i.v. bolus form into 21 insulin-dependent (IDDM) and 22 noninsulin-dependent (NIDDM) diabetics before and one to three months after strict glycemic control with multiple insulin injection therapy or continuous subcutaneous insulin infusion therapy. To reduce fasting blood glucose level and to obtain the same hypoglycemic stimuli, overnight insulin infusion at a basal dose was undertaken in IDDM who showed hyperglycemia before strict glycemic regulations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Mechanism of the blunted glucagon response to insulin-induced hypoglycemia in diabetics]. 354 95

We investigated the effect of treatment with biofeedback-associated progressive muscle relaxation on 10 patients with poorly controlled type I diabetes mellitus compared with 10 equivalent untreated patients. In contrast to previous studies of patients with type II diabetes, no improvement occurred in glucose tolerance after 1 wk of intensive in-hospital relaxation training or in glycohemoglobin and total daily insulin dose after 6 wk of practicing relaxation techniques at home. This and other studies suggest that this type and amount relaxation therapy may not be as useful for enhancing blood glucose control in patients with type I diabetes as in those with type II diabetes. However, subpopulations of type I diabetic patients who have demonstrated stress-induced hyperglycemia should be further investigated.
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PMID:Effects of relaxation therapy on patients with type I diabetes mellitus. 355 16

Diabetes is associated with changes in plasma lipids and lipoproteins into atherogenic direction. In IDDM these changes are small or absent if good metabolic control can be maintained. Diabetic nephropathy is, however, associated with the appearance of dyslipoproteinemia. In NIDDM plasma total and VLDL triglyceride levels are elevated, and HDL-cholesterol level is decreased, and this pattern of dyslipoproteinemia does not always respond to improved control of hyperglycemia. Abnormalities of lipoprotein metabolism, not reflected in conventional plasma lipid and lipoprotein level measurements, and glucosylation of lipoproteins and resulting alterations in lipoprotein catabolism may be of importance in the enhanced atherogenesis in diabetes. Both IDDM and NIDDM are associated with an increased frequency of hypertension, but the underlying mechanisms appear to be different. In IDDM hypertension is usually associated with the development of diabetic nephropathy and thus with a long duration of the disease. In NIDDM hypertension is often present already at the time of diagnosis, and also in IGT, the precursor stage of NIDDM, the prevalence of hypertension is already increased. Obesity explains only in part the high prevalence of hypertension in patients with NIDDM. Diabetes is known to be associated with multiple abnormalities in hemostatic factors and, although these abnormalities may contribute importantly to the increased risk of ASVD in diabetic patients, information about their real role is scanty and conflicting. The impact of general major risk factors for ASVD, elevated plasma cholesterol, elevated blood pressure, and smoking, on the risk of ASVD appears to be similar in diabetics and nondiabetics. Only a relatively small proportion of the excessive occurrence of ASVD in diabetics can, however, be explained by the effects of diabetes on the levels of general risk factors for ASVD. This proportion mediated through the effects of diabetes on risk factors is larger in female diabetics than in male diabetics. The major proportion of the excess of ASVD in diabetics remains, however, unexplained and must be due to effects of diabetes itself through mechanisms that are incompletely understood.
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PMID:Diabetes and atherosclerosis: an epidemiologic view. 355 30

The successful prevention of spontaneous autoimmune diabetes in biobreeding (BB) rats--the closest animal model to human type I diabetes mellitus--by daily administrations of cyclosporine (CsA) has prompted clinical trials of CsA immunosuppression in human diabetes. Although remissions from hyperglycemia have been achieved in human subjects, nephrotoxicity and recurrence of diabetes after discontinuation of CsA have been observed. Therefore we studied the biologic efficacy of intermittent administration of CsA, a theoretically less dangerous immunosuppressive protocol, in the prevention of spontaneous diabetes in the BB rat. Beginning at 30 to 49 or 50 to 55 days of age, treated animals (n = 86) received daily injections of CsA (15 mg/Kg) for 2 weeks (induction phase) and then twice weekly (maintenance phase) until 160 days of age. A third group of animals (n = 31) received daily CsA for 14 days only. Control littermates (n = 121) were not injected. All animals were followed to 275 days of age. Intermittent administration of CsA was determined to be a biologically effective regimen in the prevention of spontaneous diabetes in the BB rat. Blood levels of CsA and the major CsA metabolites were undetectable intermittently during the course of therapy. Major complications associated with CsA immunosuppression (nephrotoxicity, malignancy, and infection) were not associated with the intermittent CsA protocol. We conclude that spontaneous diabetes can be delayed and often permanently prevented by intermittent administration of CsA. This immunosuppressive regimen deserves further consideration as a biologically effective, but theoretically less toxic, therapeutic regimen.
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PMID:Prevention of diabetes in BB rats by intermittent administration of cyclosporine. 361 13

We studied 24 skin biopsies of the hand in 24 IDDM patients followed at the National Institute of Endocrinology (NIE). Biopsies of 7 healthy individuals were used as controls. The diabetics were divided into two groups, with limited joint mobility (LJM) and without LJM. We compared the different structural components of the skin, and their changes; we used quantitative, semi-quantitative and qualitative methods. We found that patients with LJM had a greater levelling, less rete pegs and dermal papillae (p less than 0.05), increased alteration of the mucopolysaccharides distribution (p less than 0.005), higher frequency of alterations of the elastic fibers (p less than 0.05) and collagen (p less than 0.005), vessel enlargement (p less than 0.025) acquiring cord shape, and reduction of the vessel lumen (p less than 0.005) in comparison with patients without LJM and controls. This could be a consequence of the chronic hyperglycemia from childhood that affects the structure, architecture and function of collagen fibers. Genetic and immunologic studies could help to elucidate the mechanisms of this alteration.
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PMID:Histological and histochemical skin changes in insulin-dependent diabetic patients with and without limited joint mobility. 363 May 33

Muscle capillary basement membrane width is a sensitive marker for the presence of diabetic microangiopathy. Studies have indicated that genetic factors and alterations in glucose metabolism influence muscle capillary basement membrane width. To define the role of these factors we have measured muscle capillary basement membrane thickness in controls, insulin dependent diabetics, and individuals with diabetes secondary to the ingestion of Vacor, a rat poison, which results in hyperglycemia. Hemoglobin A1 concentrations were increased in both diabetic groups, but hemoglobin A1 levels and the duration of diabetes were similar in the two diabetic groups. The muscle capillary basement membrane width was increased to a similar extent in the insulin-dependent diabetics (control, 1,781 +/- 46 vs. IDD, 2,287 +/- 144 A, P less than 0.001) and in the Vacor diabetic group (2,320 +/- 149 A, P less than 0.001). In the insulin-dependent diabetic group, 63% of the patients had a muscle capillary basement membrane width greater than two standard deviations above the mean of the controls, while in the Vacor diabetic group this figure was 56%. Despite the relatively short duration of diabetes (6.2 +/- 0.3 yr), 44% of the Vacor diabetic patients had retinopathy and 28% had proteinuria. The present study provides strong evidence that even in the absence of genetic diabetes mellitus, hyperglycemia or some other abnormality related to insulin lack can cause microvascular changes.
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PMID:Muscle capillary basement membrane width in patients with vacor-induced diabetes mellitus. 372 72

In conclusion, there is considerable data documenting the presence of resistance to insulin-stimulated glucose uptake in patients with either IDDM or NIDDM. However, the characteristics of this metabolic abnormality are quite different in the two syndromes. In the case of IDDM the insulin resistance appears to be secondary to the state of altered carbohydrate homeostasis, is directly proportional to the severity of fasting hyperglycemia, and can be abolished by achievement of metabolic control. As a corollary, it seems reasonable to suggest that resistance to insulin-stimulated glucose uptake is not a primary defect in the pathogenesis of IDDM. Nevertheless, the presence of insulin resistance in the poorly-controlled patient with IDDM may be of great clinical relevance, and contribute to the difficulty in effective treatment of this syndrome. In contrast, resistance to insulin-stimulated glucose uptake does not seem to be a simple function of severity of hyperglycemia in patients with NIDDM, and significant insulin resistance can exist in these patients in association with only mild carbohydrate intolerance. Furthermore, although the decline in insulin-stimulated glucose disposal present in patients with significant fasting hyperglycemia can be increased by instituting excellent metabolic control with exogenous insulin, it cannot be restored to normal. These observations suggest that some component of the insulin resistance in NIDDM is similar to that in IDDM, and is secondary to the state of poor metabolic control. On the other hand, it also suggests that another component of the insulin resistance in NIDDM is primary, and most likely related to the pathogenesis of this syndrome. Obviously, there is a great need to define the mechanism of this unexplained portion of the insulin resistance of NIDDM.
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PMID:Insulin-stimulated glucose disposal in patients with type I (IDDM) and type II (NIDDM) diabetes mellitus. 389 61

Insulin resistance is a characteristic feature of non-insulin dependent diabetes mellitus (NIDDM) due to target tissue defects in insulin action. Abnormalities of cellular insulin action can be divided into receptor and post-receptor defects. Patients with impaired glucose tolerance are insulin resistant due to decreased insulin receptors resulting in decreased insulin sensitivity and rightward shifted in vivo dose response curves. Patients with NIDDM are insulin resistant due to a combination of receptor and post-receptor defects. The greater the severity of the diabetes (greater fasting hyperglycemia) the greater the post-receptor defect, and in those patients with more significant fasting hyperglycemia the post-receptor defect is the predominant abnormality leading to the insulin resistant state. At least one of the abnormalities underlying this post-receptor defect involves a decrease in glucose transport system activity in freshly isolated adipocytes. This defect in glucose transport, is not expressed in cultured fibro-blasts, indicating that the abnormality in glucose disposal seen in vivo and in glucose transport seen in freshly isolated cells is an acquired phenomenon. Consistent with this, the post-receptor defect is partially reversible by insulin therapy, which leads to a 50-70% reversal of the reduced rates of in vivo glucose disposal and in vitro glucose transport. Insulin resistance also exists in poorly controlled IDDM patients, due to a postreceptor defect in insulin action. This insulin resistance is not present in well controlled IDDM patients, and is completely reversible when poorly controlled patients are treated with intensive insulin therapy. Insulin is produced in the pancreatic beta cell as the primary biosynthetic product preproinsulin. This peptide is rapidly converted to proinsulin (MW approximately 9000). Proinsulin is converted to insulin (MW approximately 6000) plus C-peptide in the secretory granule with a small amount (approximately 5 percent) of the proinsulin remaining unconverted. After a brief time in the peripheral circulation (half-life six to 10 minutes), insulin interacts with target tissues to exert its biologic effects. One of insulin's major biologic effects is the promotion of overall glucose metabolism, and abnormalities of this aspect of insulin action can lead to a number of important clinical and pathophysiologic states including Type II diabetes, also known as non-insulin-dependent diabetes mellitus (NIDDM). Since insulin travels from the beta cell through the circulation to the target tissues, abnormalities at any of these loci can influence the ultimate action of the hormone. These abnormalities, all
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PMID:Insulin resistance in non-insulin dependent (type II) and insulin dependent (type I) diabetes mellitus. 389 63

During constant insulin infusion (0.15 mU X kg-1 X min-1) from 12 PM to 8 AM in 10 IDDM patients previously rendered euglycemic (Biostator), plasma glucose (5.4 +/- 0.2 mmol/L at 12 PM) increased by 3:30 AM and reached 12.1 +/- 1.6 mmol/L at 8 AM (P less than 0.001). Glucose production also increased at 3:30 AM; hyperglycemia, glucose utilization did not increase until after 5 AM. Plasma growth hormone (12 PM to 4 AM), cortisol (after 3:30 AM), noradrenaline (after 1:30 AM), and adrenaline (after 3:30 AM) but not glucagon increased significantly overnight, although plasma adrenaline and noradrenaline remained at subthreshold levels. Insulin clearance increased (approximately 25%, P less than 0.05) but only after 7 AM, resulting in a 4 mU/L decrease in plasma insulin. A significant correlation was found between increases in plasma glucose and increases in glucose production (r = 0.74, P less than 0.05) which in turn were significantly correlated with nocturnal peaks in plasma growth hormone (r = 0.66, P less than 0.05). From the sequence of events observed, we conclude that the Dawn Phenomenon in IDDM begins earlier than is currently thought (approximately 3:30 AM), that it is due to both accelerated glucose production and impaired glucose utilization, and that nocturnal increases in sympathetic nervous system activity and/or growth hormone secretion, but not changes in secretion of cortisol, adrenaline and glucagon or changes in insulin clearance, may be of pathogenetic importance.
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PMID:Sequence of events during development of the dawn phenomenon in insulin-dependent diabetes mellitus. 390 50

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