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

The glucagon-secreting A cell is a vital component of the organ system which regulates the distribution of fuel--the islets of Langerhans. Bihormonal control of glucoregulation through a push-pull system maintains the glucose concentration of extracellular fluid within narrow limits irrespective of glucose flux rates through relative equality of glucose influx and efflux. This equality requires appropriate secretion mixtures of the biologic antagonists, insulin and glucagon, directed by a glucose sensor. In severe diabetes, there are virtually no B cells and A cells are in contact largely with other A cells and their glucose-sensing capacity is lost. The A cell hypersecretes and in most juvenile type diabetics aggressive therapy with insulin fails to restore it to normal. Glucagon is a factor in the development of endogenous hyperglycemia, and ketoacidosis. Its suppression may provide a possible approach in the future pharmacologic management of diabetic hyperglycemia.
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PMID:Role of glucagon in diabetes. 40 69

The effect of an oral dose of 1 gm. L-dopa either without or after a concomitant oral administration of 100 gm. glucose on the plasma level of pancreatic glucagon, plasma immunoreactive insulin (IRI), and plasma growth hormone (GH) was assessed in eight normal and 10 insulin-treated diabetic subjects. In the normal group the stimulatory effect o L-dopa on pancreatic glucagon release was reconfirmed. Moreover, in the diabetics essentially the same plasma glucagon increase after drug administration was found, such a response being inhibited in both groups by glucose. The increase of plasma GH after L-dopa in both healthy persons and diabetics and the inhibition of this response by glucose in healthy subjects was reconfirmed. Furthermore, the same effect of exogenous glucose on the L-dopa induced GH release was observed in diabetics. It may be concluded that glucagon may play a pathogenetic role in the worsening of parkinsonian diabetic patients during the treatment with L-dopa and that diabetic hyperglycemia per se seems to be insufficient for an inhibition of the release of both glucagon and GH AFTer L-dopa.
Diabetes 1978 Apr
PMID:Effect of glucose on the glucagon response to L-dopa in normal and diabetic subjects. 64 Feb 44

To determine whether somatostatin, an inhibitor of glucagon and growth hormone secretion, might be useful as an adjunct to insulin the management of diabetic hyperglycaemia, seven insulin-requiring diabetic men were given somatostatin (100 microgram/h, IV) continuously for 3 days after their diabetes had been treated intensively by diet and insulin on a metabolic ward. During infusion of somatostatin and despite reduction in average insulin dose exceeding 50%, there was improvement in diabetic control as assessed by postprandial hyperglycaemia, 24-h glycosuria and the average daily serum glucose level and its fluctuation; when somatostatin was discontinued, but insulin doses held constant, diabetic control rapidly worsened. No adverse effects were observed. These results indicate that somatostatin plus insulin can be a more effective regimen than insulin alone in controlling diabetic hyperglycaemia. A longer acting and more selective somatostatin preparation may prove useful as an adjunct to insulin in the management of diabetes.
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PMID:Clinical evaluation of somatostatin as a potential ajunct to insulin in the management of diabetes mellitus. 90 78

Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy. This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin. Glucagon suppression could improve therapeutic glucoregulation in diabetes.
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PMID:Glucagon: role in the hyperglycemia of diabetes mellitus. 108 99

In order to elucidate the association between hyperglycemia and the vascular complications of diabetes, the effects of high glucose concentrations on the migration, proliferation and tube formation of bovine carotid artery endothelial cells were investigated. Cells treated with 16.7 and 33.3 mM glucose for 6 days showed 1.69- and 1.75-fold increase in serum-induced migration compared with cells treated with 5.6 mM glucose (p less than 0.05). The effect of glucose on cell proliferation was affected by serum concentration. When this was below 0.5%, a high glucose concentration stimulated cell growth to a maximum of 1.73 times that at a serum concentration of 0.05% (p less than 0.01) whereas at a serum concentration of 10%, growth was inhibited (p less than 0.05). Tube formation was studied by culturing the cells between two layers of collagen gel. Ultrastructurally, tubular structures were composed of one to several endothelial cells containing pinocytotic vesicles and cytoplasmic projections, and linked by junctional complexes. A basal lamina-like structure surrounded the abluminal surface. Treatment of the cells with 16.7 and 27.8 mM glucose for 4 days stimulated tubular elongation 1.85 and 1.71 times, respectively (p less than 0.01). Other osmogenic molecules such as mannitol and sucrose did not affect tube formation. These data imply that high glucose concentrations mimicking diabetic hyperglycemia may not inhibit the repair of endothelial injury and could act as a stimulator of neovascularization.
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PMID:Effects of glucose on migration, proliferation and tube formation by vascular endothelial cells. 168 13

The paper describes results after a study of pathochemical disturbances of diabetic hyperglycemia on a model of alloxan diabetes. Sugar and amino nitrogen contents in the aqueous humor of the anterior chamber, anterior and posterior segments of the crystalline lens, the iris, ciliary body, choroid and the retina were studied and the data obtained were compared with quantitative contents of sugar and amino nitrogen in the eliminate from the eyes of experimental animals. High amounts of sugar and amino nitrogen, infrequently exceeding 2-3 times in controls, were found to appear in the aqueous humor of the anterior chamber, the crystalline lens, the vitreous body. In all tests the sugar and amino nitrogen contents in the posterior segment of the lens was 10-12% higher than in its anterior segment. The data obtained about accumulation of sugar and amino nitrogen mainly in tissues and media of the eye (the lens, the vitreous) affected by diabetic process already at its early stages widen the knowledge about pathogenesis of the process and peculiarities of its pathochemistry.
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PMID:[The pathochemistry of the diabetic process in the eye based on data on experimental hyperglycemia (alloxan diabetes)]. 258 77

This study examined the induction of electroretinogram abnormalities in hyperglycemia and the possible role of increased polyol pathway activity in the development of these changes. Both diabetic hyperglycemia and galactosemia caused the prolongation of peak latencies and in some cases a reduction in the amplitudes of oscillatory potentials on the b-wave. Diabetic hyperglycemia-associated abnormalities were prevented and normalized by insulin or ADN-138, an aldose reductase inhibitor. Galactosemia-induced abnormalities were inhibited by ADN-138, and were reversed either by ADN-138 treatment or by withdrawal of galactose from the diet. Polyol accumulation was prevented by insulin or ADN-138, and the elevated polyol level was reversed by insulin, ADN-138, or withdrawal of galactose in diabetic hyperglycemia and/or galactosemia. These results suggest that the increased polyol pathway activity in the hyperglycemia may be involved in the development of electroretinogram abnormalities similar to those in human diabetes; therefore, ADN-138 could be a useful drug for therapy of retinopathy in the early diabetic stage.
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PMID:The development of electroretinogram abnormalities and the possible role of polyol pathway activity in diabetic hyperglycemia and galactosemia. 328 32

Because of their remarkable longevity, lens crystallins undergo a substantial amount of glycation (non-enzymatic glycosylation) during diabetic hyperglycemia. These post-translational modifications have the potential to disrupt the structural and functional properties of the lens crystallins and contribute to the formation of cataracts. Streptozotocin-induced diabetic rats were used to study the relationship between glycation of lens proteins and the formation of insoluble high-molecular-weight (HMW) aggregates believed to be responsible for cataract formation. After the onset of diabetes, cataracts developed in about 12- to 13 weeks. The animals were followed in this manner until cataracts developed and for an additional 63 days. Five control and five diabetic rats were killed every 3 weeks and lenses removed. Levels of glycated protein and glycated amino acids in lenses from each animal were examined by affinity chromatography. In addition, the changes in crystallin composition and development of HMW aggregates were monitored by molecular-sieve HPLC techniques. As diabetic hyperglycemia continued there was a linear increase in glycated protein in both the soluble and insoluble fractions. This increase was paralleled by an increase in the soluble HMW and insoluble HMW aggregates. Other changes included a decrease in reactive sulfhydryls which indicates an increase in disulfide bond formation. The gamma-crystallin levels also decreased in a linear fashion during the hyperglycemic pre-cataract and cataract stages. It appears that the glycation of lens crystallin, the disappearance of reactive sulfhydryls and the formation of HMW aggregates are interrelated.
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PMID:Progressive changes in lens crystallin glycation and high-molecular-weight aggregate formation leading to cataract development in streptozotocin-diabetic rats. 358 12

Hepatic glucose production (3H-glucose technique) and insulin-mediated glucose uptake (insulin clamp technique) were measured in 38 Type 2 (non-insulin-dependent) and 11 Type 1 (insulin-dependent) diabetic patients. Fasting plasma glucose concentration was 8.3 +/- 0.5 mmol/l in the former, and 9.6 +/- 1.3 mmol/l in the latter group; the respective fasting plasma insulin levels were 19 +/- 2 mU/l (p less than 0.005 versus 13 +/- 1 mU/l in 33 age-matched control subjects), and 9 +/- mU/l (p less than 0.01 versus 14 +/- 1 mU/l in 36 younger control subjects). In the fasting state, hepatic glucose production was slightly increased (15%, 0.1 greater than p greater than 0.05) in the Type 2 diabetic patients and markedly elevated (65%, p less than 0.001) in the Type 1 patients compared with their respective control groups. In both groups of diabetic subjects, the rates of hepatic glucose production were inappropriately high for the prevailing plasma glucose and insulin levels, indicating the presence of hepatic resistance to insulin. Basal plasma glucose clearance was also significantly reduced in both the Type 2 (34%) and the Type 1 (14%) diabetic subjects. The fasting plasma glucose concentration correlated directly with hepatic glucose production, and inversely with plasma glucose clearance. During the insulin clamp, plasma insulin was maintained at approximately 100 mU/l in all groups, while plasma glucose was maintained constant at the respective fasting levels. Total glucose uptake was reduced in both the Type 2 (4.57 +/- 0.31 versus 6.39 +/- 0.25 mg . min -1 . kg -1 in the control subjects, p less than 0.01) and the Type 1 (4.77 +/- 0.48 versus 7.03 +/- 0.22 mg . min -1 . kg -1, p less than 0.01)diabetic patients. Insulin-stimulated glucose clearance was reduced to a similar extent in Type 2 (54%) and Type 1 (61%) diabetic subjects, and correlated directly with fasting glucose clearance. These results show that insulin resistance is a common feature of both types of diabetes and can be demonstrated in the basal as well as the insulin-stimulated state. Both hepatic and peripheral resistance to the action of insulin contribute to diabetic hyperglycaemia.
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PMID:Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus. 675 15

The antinociceptive potency of morphine as determined by the tail-flick test was significantly decreased in streptozotocin (STZ)-induced diabetic mice and mice pretreated with hypertonic dextrose or fructose. STZ-induced diabetic rats and spontaneously diabetic mice were also significantly less sensitive to the antinociceptive effects of morphine in the tail-flick test. Hypoglycemic mice were significantly more sensitive to morphine. Insulin-reversal of dextrose- and STZ-induced diabetic hyperglycemia returned sensitivity to morphine-induced antinociception to control values. Pretreatment with hypertonic 3-O-methylglucose (a nonmetabolizable sugar) had no effect on morphine potency. The ability of morphine to inhibit phenylquinone-induced writhing was attenuated in STZ-induced diabetic mice. Mice receiving various pretreatments (STZ-induced diabetes, STZ-induced diabetes plus insulin, dextrose, fasting or fasting plus insulin) were subjected to analyses of their serum glucose levels, serum insulin levels and brain glucose lvels. From these data, it appeared that only hyper- or hypoglycemia correlated (inversely) with changes in the potency of morphine. It is hypothesized that the diabetes-induced hyperglycemia is responsible for selectively affecting the potency of morphine.
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PMID:Narcotics and diabetes. I. The effects of streptozotocin-induced diabetes on the antinociceptive potency of morphine. 701 15


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