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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of intraperitoneal administration of aminophylline on the rate of hepatic glucose production and peripheral uptake (Ra and Rd) was studied in normal and in adrenodemedullated and reserpinized rats by using the primed constant infusion of Glucose-2-3H. In normal rats, the dose of 100 mg. per kilogram of aminophylline produced a marked increase of Ra and Rd. Since Ra rose more rapidly than Rd did initially, hyperglycemia developed. Thereafter, glucose production and uptake increased to nearly the same extent, and a new steady state was reached at plasma glucose levels almost twice those of the baseline. Smaller and transient modifications were observed after the administration of 20 mg. per kilogram of aminophylline. With the higher dose, insulin levels markedly rose (reaching a tenfold peak above the basal value) while minor increments were observed with the lower dose. In a group of normal rats which were given glucose (10 mg. per kilogram per minute) in order to achieve a degree of hyperglycemia comparable to that brought about by the higher dose of aminophylline, an almost identical enhancement of glucose uptake was recorded. However, insulin levels were much higher in aminophylline-treated rats as compared to normal rats. From these finding it was concluded that aminophylline induces resistance to insulin effect. When aminophylline was injected into demedullated rats pretreated with reserpine, at the dose of 100 mg. per kilogram, a marked enhancement of Ra, and consequently of glycemia, was recorded initially; later, severe hypoglycemia developed depending on both a progressive exhaustion of hepatic glucose production and a marked increase of glucose utilization. Insulin levels dramatically increased in these experiments. These results suggest that aminophylline directly increases glucose production by the liver and insulin secretion. The simultaneous activation of the sympathetic system blunts the insulin response and counteracts the restraining effect of insulin on the liver and the stimulatory effect of insulin on overall glucose uptake as well.
Diabetes 1975 Mar
PMID:Effects of theophylline on glucose kinetics in normal and sympathectomized rats. 111 48

Glucagon-like peptide-I(7-37) [GLP-I(7-37)] is an intestinal peptide hormone that is released in response to oral nutrients and that potently augments glucose-mediated insulin secretion. GLP-I(7-37) has potent insulin-releasing activities in vivo in response to oral nutrients, in situ in the isolated perfused pancreas, and in vitro in cultured pancreatic B-cells. As such GLP-I(7-37) is a potent hormonal mediator in the enteroinsular axis involved in the regulation of glucose homeostasis. We now show that in addition to stimulating the release of insulin, GLP-I(7-37) stimulates proinsulin gene expression at the levels of gene transcription and cellular levels of proinsulin messenger RNA as well as the translational biosynthesis of proinsulin. These findings of the positive anabolic actions of GLP-I(7-37) on the synthesis of insulin in B-cells support the notion that GLP-I(7-37) may be of therapeutic use in stimulating the production of insulin in patients with noninsulin-dependent diabetes mellitus and that overproduction of insulin with subsequent hypoglycemia will not occur in response to the administration of GLP-I(7-37). Furthermore, these positive actions of GLP-I(7-37) on insulin production obviate the possibility of B-cell exhaustion in response to such a potent secretagogue.
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PMID:Insulinotropic hormone glucagon-like peptide-I(7-37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. 130 25

Acanthosis nigricans is a skin lesion characterized by thickening and apparent darkening of the keratin layer of the skin, usually on the neck and axillae. Recent studies reveal that this disorder is directly associated with hyperinsulinemia. A major implication of hyperinsulinemia is insulin resistance--a primary factor in the development of type II diabetes mellitus. Prolonged hypersecretion of insulin presumably leads to pancreatic exhaustion and subsequent glucose intolerance that can progress to type II diabetes. Prospective studies of individuals with acanthosis nigricans have shown very high prevalence rates of type II diabetes. Prevalence studies among adolescents have shown that the lesion appears early in life and is a common finding in some ethnic groups. These data suggest that acanthosis nigricans is an easily detected empirical marker for elevated risk of type II diabetes. The lesion can appear long before the onset of glucose intolerance. Thus, including acanthosis nigricans screening in a comprehensive disease-prevention program can help identify people at risk for type II diabetes prior to the actual onset of glucose intolerance, as well as individuals with undiagnosed diabetes. Interventions that reduce insulin resistance include weight loss and regular physical activity.
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PMID:Assessment of patients with acanthosis nigricans skin lesion for hyperinsulinemia, insulin resistance and diabetes risk. 154 62

The passive (tilting) orthoclinostatic test was performed on 44 young subjects affected by type 1 insulin-dependent diabetes. In 11 cases the test was repeated after a 3-4 years interval. The results, compared with age matched controls, showed in the diabetic patients a supersensitivity of the two antagonist systems, increasing with age and duration of the disease, up to an overexcitability and a functional exhaustion. It would thus seem that diabetic dysautonomia involves not only the peripheral nervous system but also the hypothalamic centers, with an impoverishment of the capacity of self-regulation. The hypersympathicotonus in diabetic young patients seems to be only apparent, as a result of the hypersensitivity of an overstimulated system.
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PMID:[Study of neurovegetative function in type 2 diabetes mellitus in childhood]. 180 74

According to their general appearance, the ultrastructural morphology of their organelles and their functional status, B cells can be divided into dark, unresponsive B cells with condensed mitochondria and narrow RER-cisternae, and pale activated B cells with orthodox mitochondria and distended RER. In control rats, during a three hour glucose infusion experiment, there is a shift from a majority of dark B cells to a majority of pale B cells, and a decrease in the proportion of dark and mixed islets in favour of the pale islets. No degranulation however (dark and light granules) occurs. In adult youngsters of severely diabetic mothers, known to be hyperresponsive to glucose stimulation, a more important mass of pale activated B cells is present in basal conditions, and is not augmented by stimulation. Dark and mixed islets are scarce in these animals and some degranulation occurs. The data illustrate that in control and in hyperresponsive rats, the B cells manage very well, to meet the increasing demand of insulin without any signs of exhaustion or damage. The data confirm in vivo, and at the morphological level, the concepts of functional heterogeneity and of dose-dependent recruitment of pancreatic B cells. Moreover functional heterogeneity of islets is suggested.
Diabetes Res 1991 Sep
PMID:Morphometric evaluation of B-cell function during glucose infusion in control and hyperresponsive rats. 182 40

Most incidence studies indicate that baseline plasma glucose, either fasting or post-glucose load, is the best predictor of progression to non-insulin-dependent diabetes mellitus (NIDDM)--the higher the level, the higher the risk. Elevated serum insulin concentrations in the presence of normal fasting plasma glucose levels reflect the presence of insulin resistance and they have also been shown to predict deterioration to NIDDM in a number of populations. Hyperinsulinaemia is a notable characteristic of populations with a high prevalence of NIDDM such as Micronesian Nauruans, American Pima Indians, Mexican-Americans and Asian Indians. In Nauruans and Pima subjects with normal glucose tolerance, those with higher post-load (2-hour) serum insulin at baseline were more likely to progress to either impaired glucose tolerance (IGT) or NIDDM. Conversely, amongst subjects with IGT, progression to NIDDM was predicted by lower (but still high relative to normal) baseline insulin responsiveness. Similar results for subjects with IGT have been described in Japanese. It appears from longitudinal studies that baseline insulin and glucose levels explain much of the association of obesity with risk of NIDDM. It remains to be resolved whether obesity itself may be a manifestation of an underlying defect (such as primary hyperinsulinaemia) which leads to both obesity and NIDDM. The possible sequence of events for the development of NIDDM includes a genetic defect resulting in hyperinsulinaemia and/or insulin resistance and leading ultimately to secondary pancreatic exhaustion with an insulin secretory defect which may also be genetically determined or the result of glucotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperinsulinaemia is a predictor of non-insulin-dependent diabetes mellitus. 193 64

Twelve healthy men with IDDM participated in a 12-week walking/jogging exercise program. Pre- and postexercise assessment of dietary intakes, body composition, biochemical measures, and exercise performance indicators were completed. Subjects exercised either 3 or 5 days per week for 1 hour at 60% to 80% of estimated maximal heart rate. Dietary intakes showed a voluntary reduction in fat intake as a percent of total energy from 40% +/- 7% (mean +/- SD) to 37% +/- 8% (P = .053). No change occurred over time in body composition measures except for a significant reduction in the waist-to-hip ratio from 0.87 +/- 0.04 to 0.86 +/- 0.04 (P = .007). Fasting serum glucose and lipid levels did not change over time. Exercise capacity improved, as shown by an increased time to exhaustion on a treadmill run from 7.9 +/- 3.7 minutes to 9.7 +/- 3.8 minutes (P less than .001); and a lower heart rate at a constant work load--from 183 +/- 18 beats per minute preexercise to 175 +/- 20 beats per minute postexercise (P = .022). The study showed that healthy male subjects with IDDM can benefit from regular exercise with a redistribution of body fat and improved exercise capacity.
Diabetes Educ
PMID:Benefits of exercise training for men with insulin-dependent diabetes mellitus. 201 25

The role of insulin in the control of triacyglycerol (TG) in different types of skeletal muscle has not been fully recognized so the aim of the present study was to fill this gap. The experiments were carried out on control rats, those fed with olive oil or fed with the oil and treated with insulin and on streptozotocin diabetic animals at rest and there after exercise till exhaustion. The level of TG was measured in the white and red layers of the vastus lateralis, the soleus and the diaphragm. It was found that acute feeding with olive oil had no effect on TG level in either muscle type examined. Insulin administered to rats fed with oil increased TG level in the red vastus. Streptozotocin diabetes caused an increase in TG level in muscles with high oxidative potential. Exercise lowered the level of TG only in the red vastus of the diabetic rats. It is concluded that insulin may increase muscle TG level. Accumulation of TG in muscles of rats with acute diabetes is likely to be a result of the high plasma free fatty acid concentration. Acute insulin deficiency did not affect the muscle TG response to exercise.
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PMID:The role of insulin in the control of triacyglycerol (TG) in the rat skeletal muscles. 213 89

Although controversies remain as to the usefulness of sulfonylureas, most evidence is in favor of their use in many if not patients with non-insulin-dependent diabetes mellitus. When used properly, sulfonylureas improve insulin secretion and action, and these effects may be maintained for years. If combined with hypocaloric dietary regulation, rapid- and short-acting sulfonylureas may help patients reach and maintain euglycemia without provoking chronic hyperinsulinemia or weight increase. There is no evidence that sulfonylurea treatment causes beta-cell exhaustion; instead, the antihyperglycemic effect helps improve beta-cell function. Sulfonylurea "failures" are often dietary failures or may be due to late introduction of these drugs, i.e., when beta-cell function is already attenuated. Desensitization of the insulinotropic effect of sulfonylureas may occur but might be avoided by discontinuous (less than 24 h/day) sulfonylurea exposure, i.e., once-daily administration of a short-acting sulfonylurea in a moderate dose. The most important adverse effect of sulfonylureas is long-lasting hypoglycemia, which may lead to permanent neurological damage and even death. This is mainly seen in elderly subjects who are exposed to some intercurrent event, e.g., acute energy deprivation or a drug interaction, i.e., aspirin. Long-acting sulfonylureas may be more likely to promote long-lasting hypoglycemia. The dose-response relationships of sulfonylureas have been poorly investigated, and sulfonylurea therapy should always be initiated and maintained at the lowest possible dose.
Diabetes Care 1990 Aug
PMID:Sulfonylureas. Why, which, and how? 220 39

The trace element vanadium exerts insulinlike effects in vitro and decreases hyperglycemia in insulin-deficient animals. This study examined whether vanadate can improve glucose homeostasis in genetically obese hyperglycemic insulin-resistant ob/ob mice, which present metabolic abnormalities similar to those of human non-insulin-dependent diabetes. Sodium orthovanadate (0.3 mg/ml) was administered for 7 wk in H2O. Vanadate treatment induced a fall in fed and fasted plasma glucose and insulin levels and improved tolerance to oral glucose; the stimulated glucose area was decreased by 65%, and an early peak of insulin secretion was restored. During an intravenous glucose tolerance test, the glucose disappearance rate was twofold higher in vanadate-treated mice, and the reappearance of a significant insulin response was also observed. Moreover, vanadate produced a twofold increase in hepatic glycogen content and prevented the exhaustion of pancreatic insulin stores. The hypoglycemic response to exogenous insulin was similar in control and treated mice. In vitro experiments showed that basal glucose oxidation by hemidiaphragms was 32% higher in vanadate-treated mice than in controls, although stimulation by insulin was similar in both groups. In conclusion, oral vanadate caused a marked and sustained improvement of glucose homeostasis in diabetic insulin-resistant mice by exerting an insulinlike effect on peripheral tissues and apparently preventing the exhaustion of pancreatic insulin stores.
Diabetes 1990 Nov
PMID:Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate. 222 6


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