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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 normal individuals, insulin regulates lipoprotein metabolism. It increases hepatic triglycerides (TG) secretion and makes VLDL and chylomicrons post prandial removal easy by stimulating adipose tissue lipoprotein lipase (LPL). Insulin activity and cholesterol rich lipoprotein is more complicated: by its action on VLDL and chylomicrons turn-over, it influences LDL and HDL formation. It regulates cellular cholesterol pool at different levels: stimulation of LDL receptor, but also of HMG CoA reductase. Controlling LCAT, in participates in cholesterol removal by HDL. In insulin dependent diabetes, lack of adipose tissue LPL stimulation augments triglycerid-rich lipoproteins, by slowing their catabolism, resulting in a weak increase of LDL and a lowering of HDL. In non insulin dependent diabetes with hyperinsulinism, VLDL are elevated because of insulin stimulation of triglycerid hepatic production. LDL are increasing. HDL status remains discussed: HDL cholesterol is low but HDL triglycerid is high, there is no known disturbance of apo A level. In the two types of diabetes, although mechanism is different, perturbation of lipoprotein metabolism may account for the atherogenicity of this disorders.
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PMID:[Insulin and the metabolism of lipoproteins]. 634 30

The binding of 125I-insulin was determined using erythrocytes obtained from 11 subjects with Type I diabetes mellitus treated with continuous subcutaneous infusions of insulin for 1 year or more. The binding characteristics were compared to those for erythrocytes isolated from 12 normal subjects and 10 subjects with Type I diabetes mellitus treated with conventional daily injections of insulin. The total binding of 125I-insulin, receptor concentration, and high and low affinity binding constants were estimated using washed erythrocytes obtained from fasted subjects. The mean total specific binding for subjects treated with continuous subcutaneous infusion did not differ from that for conventionally treated diabetic subjects but was slightly lower than that for normal subjects at p less than 0.05. Receptor concentration did not vary significantly between the groups. High and low affinity binding constants were slightly lower in the group treated with continuous subcutaneous infusion. Both basal and diurnal plasma levels of free immunoreactive insulin were slightly but significantly elevated in both groups of diabetic subjects compared to that in normal subjects. Thus, in spite of the greater biological effectiveness of the continuous insulin infusion program in terms of glycemic control, the insulin-binding parameters, as well as the estimates of plasma free immunoreactive insulin levels, are consistent with modest and comparable degrees of hyperinsulinemia with both treatments.
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PMID:Insulin-binding to erythrocytes in type I diabetes mellitus: effects of continuous subcutaneous infusion of insulin. 638 Aug 57

New dimensions have been acquired in the physiopathology of insulin-resistant syndromes, by measurement of insulin receptors and advances in knowledge of their structure and function. The insulin-resistance of obese subjects and non-insulin dependent diabetics is related to both a reduction in the number of receptors, responsible for diminished sensitivity to insulin, and alterations in the action of the hormone at the post-receptor stage, with resulting suppression of the maximal response to insulin. The number of receptors varies as a function of blood insulin levels, hyperinsulinism being associated with a reduction in their number (negative feed-back). Post-receptor stages appear to be particularly sensitive to either absolute (insulin-dependent diabetes) or relative (non-insulin dependent diabetes) insulinopenia. The rare syndromes of extreme insulin resistance, often accompanied by acanthosis nigricans, represent a heterogeneous collection divisible into 3 sub-groups. In type A there is reduced insulin binding related to a possible primary anomaly (genetic) of the receptor. Type B is characterized by the presence of serum auto-antibodies directed against the receptor, while in type C the anomalies exist at the post-receptor stage. Insulin accelerates degradation of its specific receptor, a mechanism capable of explaining (at least partly) the negative feed-back control of the receptor by the hormone. The insulin-receptor complexes undergo intracellular transfer and a return to the plasmic membrane, but possible physiopathological implications of this movement have not been established. The receptor includes two principal glycoprotein subunits; alpha (130 kilodaltons) and beta (95 kilodaltons).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Insulin resistance. Physiopathological and biochemical aspects]. 639 63

Using a selective immunochemical method, the activities of postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were measured in 7 children with newly diagnosed IDDM, 39 on a conventional subcutaneous insulin regimen (CSC), and 11 children receiving continuous subcutaneous infusion of insulin (CSII). The newly diagnosed untreated patients frequently had hypertriglyceridemia and a decreased serum HDL-cholesterol level, while they showed a mild, but not significant increase of the serum total cholesterol level. The insulin-treated patients (both on CSC and on CSII) had serum lipid levels similar to those in controls. LPL activity was decreased in untreated patients, and insulin treatment resulted in an increase in the LPL activity with a concomitant normalization of serum triglyceride and HDL-cholesterol levels. In contrast to the patients on CSII who had normal LPL activity, patients on CSC had an increased LPL activity. This may have been due to peripheral hyperinsulinemia. HTGL activity did not show any increase during the time of improved diabetic control. In conclusion; (1) serum lipid levels were normal both in the patients on CSC and CSII. (2) LPL activity was normal on CSII, but was increased on CSC and decreased in untreated patients.
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PMID:Serum lipids and postheparin plasma lipase activity in Japanese children with ketosis-prone diabetes mellitus. 644 Mar 12

This paper reviews and integrates a number of experiments which suggest the existence of a vicious cycle. In this cycle hypertriglyceridemia can lead to insulin resistance even without concomitant obesity or non-insulin dependent diabetes. This insulin resistance may be the basis for the hyperinsulinemia response to a glucose challenge. The hyperinsulinemia can stimulate VLDL-triglyceride production. This increase in production, if it is not accompanied by an equivalent increase in removal, will result in hypertriglyceridemia. The whole cycle would accelerate VLDL-triglyceride turnover and may increase the supply of potentially atherogenic VLDL-remnants.
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PMID:Hyperinsulinemia and hypertriglyceridemia, a vicious cycle with atherogenic potential. 674 16

The antilipolytic effect of insulin in vitro was investigated in conditions known to be associated with resistance to the effect of insulin on glucose metabolism. Human subcutaneous adipose tissue was obtained from 14 obese subjects before and during starvation for 7 days, 12 untreated non-insulin dependent diabetics (NIDDM), 6 untreated insulin dependent diabetics (IDDM), and 10 nonobese control subjects. The tissue was incubated with and without insulin in concentration ranging from 1-10,000 microunits/ml. Responsiveness (maximum effect) and sensitivity to insulin were determined under basal induction conditions, since insulin had a bimodal effect on noradrenaline stimulated lipolysis. Under normal conditions both insulin sensitivity and insulin responsiveness were positively correlated with the basal rate of lipolysis. In obesity, IDDM and NIDDM there were no change in insulin sensitivity or in insulin responsiveness. When the obese subjects were divided into one hyperinsulinemic group (6 individuals) and one group with normal fasting serum insulin levels (7 individuals) a similar antilipolytic effect of insulin was observed in the two groups. During starvation there was a 20-fold increase in insulin sensitivity (p less than 0.01) but no change in insulin responsiveness in femoral fat and only a decrease in responsiveness (p less than 0.01) in abdominal fat. The present data supports the view that antilipolysis in human fat cells is not involved in the insulin resistance seen in obesity, starvation, diabetes and hyperinsulinemia.
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PMID:The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation. 702 6

An elevated circulating sialic acid concentration is a risk factor for cardiovascular disease. Serum sialic acid levels are elevated in NIDDM but not in uncomplicated IDDM. To study why sialic acid is increased in some types of diabetes, we assayed plasma sialic acid in various animal models of diabetes: obese (ob/ob) mice, before and after streptozotocin treatment, neonatal streptozotocin-treated (nSTZ) rats, and diabetic BB rats during and after insulin treatment. In obese mice, which exhibit moderate hyperglycemia and marked hyperinsulinemia, plasma sialic acid was decreased by 45% (fed) and 42% (fasted), compared to lean controls. Fasting reduced plasma glucose and insulin but increased sialic acid in the obese and lean mice. There was a negative correlation (r = -0.84, P < 0.001) between log plasma insulin and sialic acid in the lean and obese mice. The plasma sialic acid:globulin ratio was reduced by 35% in obese mice vs. lean controls, indicating that there may be altered sialylation of glycoproteins in obese mice. Streptozotocin treatment of obese and lean mice reduced plasma insulin but increased sialic acid. In nSTZ rats, hyperglycemia was associated with mild hypoinsulinemia, but not significantly different from control animals, and sialic acid was not altered. In diabetic BB rats, plasma glucose rose from a mean of 4.9 to 23.5 mM 48 hr after insulin withdrawal but sialic acid did not change. We conclude that an elevated plasma sialic acid level is associated with marked insulin deficiency, rather than hyperglycemia per se. The magnitude and speed of this change in sialic acid varies between species.
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PMID:Plasma sialic acid in animal models of diabetes mellitus: evidence for modulation of sialic acid concentrations by insulin deficiency. 756 86

The islets of Langerhans provide energy storage and disposal, and protection from plasma glucose excursions, especially hypoglycemia. Insulin-dependent diabetes mellitus (IDDM) results from autoimmune beta-cell damage. Prevention of IDDM has already been achieved in animal investigation and some centers are now screening and treating individuals at high risk for developing IDDM. Immunosuppressive drugs can induce transient remission of recent-onset IDDM. Intensive insulin treatment of IDDM delays the onset and slows the progression of long-term complications. Non-insulin dependent diabetes mellitus (NIDDM) is the result of beta-cell malfunction and is strongly associated with X syndrome. Diet and exercise are of undoubted importance in NIDDM prevention and treatment. Functional endocrine tumors of the pancreas (FET) are rare hormone and peptide-secreting neoplasms. These peptides may or may not occur naturally in the islets. FETs often occur with multiple endocrine neoplasia 1 (MEN 1) so that MEN-1 screening should always be performed, and extended to family members whenever diagnosed. Drugs--alcohol, insulin and sulfonilureas--are the main cause of hypoglycemia. Insulinoma is the main cause of post-absorptive organic hypoglycemia. Non islet-cell tumors seldom cause hypoglycemia. Insulinoma often is a solitary tumor, but it may be multicentric and may coexist with cell hyperplasia and nesidioblastosis. Symptoms of neuroglycopenia may be mistaken for neuropsychiatric disease. The diagnosis is based on confirmation of post absorptive hypoglycemia and hyperinsulinism. Gastrinoma causes Zollinger-Ellison syndrome (ZES) which is characterized by fulminating peptic ulcer disease. The tumor is often malignant, and it may be multicentric and may occur with cell hyperplasia and nesidioblastosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The endocrine pancreas]. 765 6

Disturbed hemodynamic reactions to insulin-induced hypoglycemia have been documented in diabetic patients and considered related to hyperinsulinemia and impairment of autonomic nervous functions. In the present study we investigated the effect on skin microcirculation of insulin-induced hypoglycemia obtained during moderate hyperinsulinemia, in 7 men with type 1 diabetes and in 8 healthy age- and sex-matched controls. The patients had all normal cardiovascular reflexes as assessed by respiratory sinus arrhythmia and Valsalva ratio. The skin microcirculation of the left fourth finger nailfold was investigated by laser Doppler fluxmetry, and the skin temperature within the same area was measured by a thermistor. Hypoglycemia was induced by a constant insulin infusion of Actrapid Human, 0.034 U kg-1 h-1 during 120 min. Plasma adrenaline, noradrenaline and pancreatic polypeptide increased significantly in both groups during hypoglycemia and the insulin levels never exceeded 50 mUl-1. A close to identical arterial hypoglycemia was obtained in the two groups 60 min after onset of insulin infusion. During hypoglycemia the control subjects revealed a significant decrease in laser Doppler flux (p < 0.025), while it was unchanged in the diabetic patients. Simultaneously, the skin temperature decreased (p < 0.05) in the controls, but was unchanged in the diabetic patients. The present study indicates that type 1 diabetic patients with normal cardiovascular reflexes have an abolished vasoconstrictor response in skin microcirculation of fingers during insulin-induced hypoglycemia, despite the fact that neurogenic and neuroglucopenic symptoms developed in these patients during hypoglycemia.
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PMID:Patients with type 1 diabetes lack vasoconstrictor response in skin microcirculation during insulin-induced hypoglycemia. 770 86

Children with IDDM have diminished glucagon responses to hypoglycemia. We evaluated possible mechanisms in 60 children and adolescents with IDDM (age 15.4 +/- 2.6 years, duration 7.8 +/- 3.5 years [mean +/- SD]) and without diabetic complications. These were: 1) suppression by hyperinsulinism, 2) autonomic neuropathy, 3) a pan-islet cell defect, and 4) a glucotoxic effect. Glucagon and pancreatic polypeptide responses to hypoglycemia (insulin bolus 0.15-0.75 U/kg) were studied after insulin withdrawal and 3 days of intensive insulin therapy. Responses to arginine and mixed meal were also studied. The control group consisted of children with non-growth hormone deficient short stature. IDDM children had lower glucagon responses to hypoglycemia than controls (p < 0.001), the response to arginine did not differ from controls, and was greater than the response to hypoglycemia (p < 0.001). Responses to hypoglycemia after insulin withdrawal and intensive therapy did not differ. Basal pancreatic polypeptide levels were lower in IDDM than in controls (p < 0.05) but responses to hypoglycemia did not differ between groups. Thus the diminished glucagon response to hypoglycemia reflects a defect in hypoglycemic recognition or response by the alpha cells.
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PMID:Abnormal alpha cell hypoglycemic recognition in children with insulin dependent diabetes mellitus (IDDM). 782 Feb 17


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