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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An 11-month-old male infant with recurrent supraventricular tachycardia (SVT) was treated with oral verapamil. Shortly thereafter he developed marked changes in behavior including lethargy, intensely increased thirst and urination, and irritability when denied fluids. "Primary" polydipsia was diagnosed following an evaluation which showed no evidence of adrenal insufficiency, diabetes insipidus, diabetes mellitus, hypercalcemia, hyperosmolality, or renal disease. The symptoms resolved 1 week after verapamil was discontinued.
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PMID:Verapamil-induced "primary" polydipsia. 852 7

Aldose reductase (EC 1.1.1.21) catalyzes the NADPH-mediated conversion of glucose to sorbitol. The hyperglycemia of diabetes increases sorbitol production primarily through substrate availability and is thought to contribute to the pathogenesis of many diabetic complications. Increased sorbitol production can also occur at normoglycemic levels via rapid increases in aldose reductase transcription and expression, which have been shown to occur upon exposure of many cell types to hyperosmotic conditions. The induction of aldose reductase transcription and the accumulation of sorbitol, an organic osmolyte, have been shown to be part of the physiological osmoregulatory mechanism whereby renal tubular cells adjust to the intraluminal hyperosmolality during urinary concentration. Previously, to explore the mechanism regulating aldose reductase levels, we partially characterized the human aldose reductase gene promoter present in a 4.2-kb fragment upstream of the transcription initiation start site. A fragment (-192 to +31 bp) was shown to contain several elements that control the basal expression of the enzyme. In this study, we examined the entire 4.2-kb human AR gene promoter fragment by deletion mutagenesis and transfection studies for the presence of osmotic response enhancer elements. An 11-bp nucleotide sequence (TGGAAAATTAC) was located 3.7 kb upstream of the transcription initiation site that mediates hypertonicity-responsive enhancer activity. This osmotic response element (ORE) increased the expression of the chloramphenicol acetyltransferase reporter gene product 2-fold in transfected HepG2 cells exposed to hypertonic NaCl media as compared with isoosmotic media. A more distal homologous sequence is also described; however, this sequence has no osmotic enhancer activity in transfected cells. Specific ORE mutant constructs, gel shift, and DNA fragment competition studies confirm the nature of the element and identify specific nucleotides essential for enhancer activity. A plasmid construct containing three repeat OREs and a heterologous promoter increased expression 8-fold in isoosmotic media and an additional 4-fold when the transfected cells are subjected to hyperosmotic stress (total approximately 30-fold). These findings will permit future studies to identify the transcription factors involved in the normal regulatory response mechanism to hypertonicity and to identify whether and how this response is altered in a variety of pathologic states, including diabetes.
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PMID:Characterization of the osmotic response element of the human aldose reductase gene promoter. 871 Sep 21

Development of atherosclerosis in diabetes patients is thought to be associated with high D-glucose-induced changes in vascular cell proliferation. This study was designed to investigate the intracellular mechanisms of altered proliferation in porcine aortic endothelial and smooth muscle cells under high D-glucose conditions. Two different technical approaches were used for determination of cell proliferation, a cell counting procedure and bromodeoxyuridine incorporation. D-Glucose diminished endothelial cell proliferation (30.3%) and increased smooth muscle cell proliferation (143%) in a dose-dependent manner. Neither D-mannitol, sucrose nor L-glucose mimicked the effect of D-glucose. Inhibition of D-glucose uptake into vascular cells by cytochalasin B prevented the effect of high D-glucose on cell proliferation. The aldose-reductase inhibitors, sorbinil and zopolrestat, little affected high D-glucose-attenuated endothelial cell proliferation, while the enhanced proliferation of smooth muscle cells was prevented by aldose-reductase inhibitors. Elevation of cellular glutathione levels yielded protection of both cell types from high D-glucose-mediated changes in cell proliferation, suggesting that high D-glucose may act via generation of oxidative species. Finally, aminoguanidine was shown to constitute a very potent inhibitor of D-glucose-induced dysfunction in vascular cell proliferation. These data suggest that high D-glucose-induced changes in cell proliferation of endothelial and smooth muscle cells are related to specific D-glucose uptake rather than hyperosmolality. Aldose-reductase seems to be mainly involved in the effect of high D-glucose only on smooth muscle cell proliferation, while in endothelial cells there is (are) other factor(s) in addition to the sorbitol pathway involved in high D-glucose-induced changes in cell proliferation.
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PMID:Intracellular mechanism of high D-glucose-induced modulation of vascular cell proliferation. 878 35

It is now generally accepted that diabetes can alter central nervous system (CNS) function. Even in the absence of overt cerebrovascular accidents or repeated hypoglycemic reactions, uncontrolled hyperglycemia is associated with cognitive changes. These changes are documented both in patients with diabetes as well as in animal models of experimental diabetes. The cognitive impairment can be ameliorated with optimization of blood glucose control. The potential causes of CNS dysfunction in diabetes can be broadly categorized as either vascular causes including changes in the blood-brain barrier and metabolic changes. The latter causes include repeated hypoglycemic episodes, hyperglycemia, hyperosmolality, acidosis, ketosis, neuroendocrine or neurochemical changes. The other contributory causes of CNS dysfunction in diabetes include the presence of hypertension, uremia, peripheral and autonomic neuropathy and multiple drug use.
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PMID:Pathophysiology of central nervous system complications in diabetes mellitus. 935 75

1. Defective leukocyte-endothelial interactions are observed in experimental diabetes mellitus. The present study investigated the effect of aminoguanidine, an inhibitor of advanced glycation end products formation, on leukocyte-endothelial interactions in alloxan-induced diabetic rats. 2. In rats anaesthetized with sodium pentobarbitone, the internal spermatic fascia was exteriorized and the microcirculation was observed by a closed-circuit TV coupled to a microscope. The number of leukocytes rolling along the venular endothelium and sticking to the vascular wall was determined after topical application of zymosan-activated plasma (1 mg ml(-1)), as well as the number of adherent and migrated cells after an irritative stimulus (carrageenan 100 microg). 3. The diabetic state decreased the number of rolling, sticking and migrated leukocytes. Pretreatment of diabetic animals with aminoguanidine (250 mg kg(-1) day(-1), for 18 days) normalized these values. To be effective, aminoguanidine had to be administered chronically, starting treatment before induction of the diabetic state. 4. The preventive effect was unrelated to the number of circulating leukocytes, or to the hyperglycaemia or to the hyperosmolality secondary to hyperglycaemia. 5. A non-dialyzed (>12,000-Mr) material in plasma from diabetic, but not normal animals, decreased the number of rolling, sticking and migrated leukocytes in recipient rats. This effect was completely abolished by chronic treatment of diabetic plasma donors with aminoguanidine. 6. The results suggest that a protein modified by glycosylation (>12 kDa) is associated with leukocyte dysfunction in diabetes mellitus and that the ability of aminoguanidine to prevent such dysfunction is related to an inhibitory effect on advanced glycation end products formation.
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PMID:Aminoguanidine and the prevention of leukocyte dysfunction in diabetes mellitus: a direct vital microscopic study. 938 5

Hyperglycemia and/or hyperosmolality may disturb calcium homeostasis in vascular smooth muscle cells (SMCs), leading to altered vascular contractility in diabetes. To test this hypothesis, the KCl-induced increases in [Ca2+]i in primarily cultured vascular SMCs exposed to different concentrations of glucose were examined. With glucose concentration in solutions kept at 5.5 mM, KCl induced a fast increase in [Ca2+]i which then slowly declined (type 1 response) in 83% of SMCs from non-diabetic rats. In 9% of non-diabetic SMCs KCl induced a slow increase in [Ca2+]i (type 2 response). Interestingly, under the same culture conditions KCl induced type 1 and type 2 responses in 47 and 35% of SMCs from diabetic rats. When SMCs from non-diabetic or diabetic rats were cultured in 36 mM glucose, KCl induced a fast increase in [Ca2+]i which, however, maintained at a high level (type 3 response). The sustained level of [Ca2+]i in the presence of KCl was significantly higher in cells cultured with 36 mM glucose than that in non-diabetic cells cultured with 5.5 mM glucose. Furthermore, the hyperglycemia-induced alterations in calcium mobilization were similarly observed in cells cultured in high concentration of mannitol (30.5 mM) or L-glucose, indicating that hyperosmolality was mainly responsible for the abnormal calcium mobilization in diabetic SMCs.
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PMID:Hyperosmolality-induced abnormal patterns of calcium mobilization in smooth muscle cells from non-diabetic and diabetic rats. 965 81

Plasma arginine vasopressin (AVP) is known to be elevated in patients with uncontrolled insulin-dependent diabetes mellitus who have plasma hyperosmolality with hyperglycaemia. Although osmotic stimuli cause an increase in nitric oxide synthase (NOS) activity as well as synthesis of AVP and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON), it is not known whether NOS activity in the hypothalamus changes in the diabetic patients who have plasma hyperosmolality with hyperglycaemia caused by insulin deficiency. Expression of the neuronal (n) NOS gene in the PVN and SON in streptozotocin (STZ)-induced diabetic rats was investigated by using in situ hybridization histochemistry and NADPH-diaphorase histochemical staining. Four weeks after intraperitoneal (i. p.) administration of STZ, male Wistar rats developed hyperglycaemia and plasma hyperosmolality. The expression of nNOS gene and NADPH-diaphorase staining in the PVN and SON remarkably increased in STZ-induced diabetic rats compared to control rats. Three weeks after administration of STZ, the diabetic rats were subcutaneously treated with insulin for 1 week, which resulted in significant suppression of the induction of nNOS, AVP and oxytocin gene expression in the PVN and SON. Furthermore, the induction of nNOS gene expression in the PVN and SON was suppressed in STZ-induced diabetic rats treated with phlorizin and diet to normalize hyperglycaemia without insulin treatment. These results suggest that upregulation of nNOS gene expression as well as AVP and oxytocin gene expression in the PVN and SON in STZ-induced diabetic rats may be associated with hyperglycaemia and plamsa hyperosmolality.
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PMID:Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats. 966 44

Patients with diabetes have an increased prevalence of premature atherosclerotic vascular disease, and alterations in plasma coagulation proteins have been incriminated as a possible cause. The roles of hyperglycemia and hyperinsulinemia in the pathogenesis of these changes are unknown. To examine the effects of prolonged hyperglycemia and of selective hyperinsulinemia on the tissue factor pathway of blood coagulation, nine healthy young men were infused with glucose to maintain levels at 11.1 mmol/l (approximately 200 mg/dl) for 18-72 h (hyperglycemia-hyperinsulinemia group). Five normal men were infused with regular insulin to maintain levels comparable to that in the previous group (900 pmol/l, approximately 150 microU/ml) and with glucose to maintain levels at 5.6 mmol/l (approximately 100 mg/dl) (euglycemia-hyperinsulinemia group). Measured were plasma activated factor VII activity (FVIIa), FVII coagulant (FVIIC) activity, FVIII coagulant (FVIIIC) activity, tissue factor pathway inhibitor (TFPI) antigen, and thrombin markers; and serum glucose, insulin, and electrolytes. Plasma FVIIa, FVIIC, FVIIIC, and TFPI rose during hyperglycemic-hyperinsulinemia but not during euglycemic-hyperinsulinemia. Markers of thrombin generation rose transiently and inconsistently during hyperglycemia-hyperinsulinemia. We concluded that in normal subjects, hyperglycemia-hyperinsulinemia induced activation of the tissue factor pathway, reflected by increases in plasma FVIIa, FVIIC, and TFPI. This activation was independent of hyperinsulinemia, hypertriglyceridemia, and hyperosmolality. The elevations in plasma coagulation factors during hyperglycemia-hyperinsulinemia, characteristic of type 2 diabetes, may constitute a potential for enhanced thrombin generation and thrombosis when triggered by exposure of tissue factor, such as during arterial plaque rupture.
Diabetes 1999 May
PMID:Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men. 1033 23

It has been reported that there is an inverse relationship between serum sodium (Na) and potassium (K) levels in patients with diabetic coma. The present study was undertaken to determine whether such an inverse relation depends upon plasma glucose levels in diabetic patients for their glycemic control. We examined two hundred and fifty-two patients with diabetes mellitus admitted to our hospital during the one-year period to control their plasma glucose levels, except for those having nephropathy or liver dysfunction. Serum Na and K, plasma glucose, and serum and urinary C-peptide levels were determined. There was a negative correlation between serum Na levels and fasting plasma glucose (FPG), and, conversely, a positive correlation between serum K levels and FPG. The changes were more evident in the patients with insulin-dependent diabetes mellitus than those with non-insulin-dependent diabetes mellitus. There was an inverse relation between serum Na and K levels and it was profoundly dependent upon plasma glucose levels in all the diabetic patients before tight control of their glycemic levels. The disorder may be based on the movement of electrolytes between intra- and extracellular spaces, dependent on the impaired insulin action as well as hyperosmolality.
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PMID:Inverse distribution of serum sodium and potassium in uncontrolled inpatients with diabetes mellitus. 1042 70

Hyperkalaemia is a frequent electrolyte disturbance connected with new knowledge and practical routine. It is developed by the disorders of the "external balance" (potassium [K] intake and output) as well as the "internal balance" (distribution of K in the extracellular and intracellular fluid compartments). Factors playing a role in it are: the upright posture, physical activity and hyperosmolality. In the hormonal regulation of K metabolism first of all beta adrenergic agents, insulin and aldosterone have significance; the first two mainly in the internal balance. Hyperkalaemia is occurring especially frequently in renal patients (in acute and chronic renal insufficiency, in dialyzed persons) in patients with diabetes, in adrenal insufficiency (Addison's disease, in selective hypoaldosteronisms and in pseudohypoaldosteronisms) in renal tubular acidosis as well as in response to various drugs (ACE inhibitors, angiotensin receptor antagonists, beta blocking agents, potassium sparing diuretics, NSAID's, anticoagulants etc.). Interactions between illness and drugs as well as between drugs and hormones may have outstanding importance in the development of hyperkalaemia. Physical activity carried out in the upright posture in the presence of hyperosmolality (water restriction together with salt or/and glucose loading) developing in pharmacological hypoaldosteronism accompanied with insulin deficiency, may be especially dangerous with respect to hyperkalaemia. To avoid life-threatening hyperkalaemia it is necessary 1. to stop cardiotoxicity with calcium; 2. to enhance K uptake by the cells by bicarbonate, insulin and beta adrenergic agents; and 3. to remove abnormal quantities of K from the body by enemas and/or ion exchange resins. The quickest and best way of treatment of hyperkalaemia is haemodialysis.
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PMID:[Hyperkalemias]. 1061 44


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