| 1. |
- Carvalho, Eugénia, 1967, et al.
(författare)
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Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.
- 1999
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 13:15, s. 2173-8
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Tidskriftsartikel (refereegranskat)abstract
- We examined the gene and protein expression of IRS 1 (insulin receptor substrate 1) in adipocytes from two groups of healthy individuals with an increased propensity for non-insulin-dependent diabetes mellitus (NIDDM): those with two first-degree relatives with diabetes and another group with massive obesity. A low expression of IRS 1 (
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| 2. |
- Eriksson, Jan W, 1959, et al.
(författare)
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Successful treatment with plasmapheresis, cyclophosphamide, and cyclosporin A in type B syndrome of insulin resistance. Case report.
- 1998
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Ingår i: Diabetes care. - 0149-5992 .- 1935-5548. ; 21:8, s. 1217-20
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Tidskriftsartikel (refereegranskat)abstract
- CASE HISTORY: A woman born in 1949 was diagnosed in 1990 with systemic lupus erythematosus. She was treated with prednisolone, and < 1 year later she presented with marked hyperglycemia. Large doses of insulin were given four times per day. Even though the patient was thin (BMI 17.4 kg/m2), very little improvement was seen. INVESTIGATIONS AND TREATMENT: Serum insulin levels were high, and a euglycemic clamp investigation confirmed severe insulin resistance. The patient's serum contained insulin receptor antibodies inhibiting insulin binding, and thus the patient had a type B syndrome of insulin resistance. After diet and exercise, glycemic control stabilized and insulin treatment was withdrawn. However, in late 1993 she was in a catabolic and hyperglycemic state even though prednisolone doses were increased and azathioprin was added. In early 1994 she was treated with plasmapheresis and cyclophosphamide i.v. Subsequently, cyclosporin A was started as a maintenance therapy in addition to azathioprin. There was a rapid and sustained clinical improvement. Since late 1994 and onward, there is no sign of diabetes or glucose intolerance and there are no demonstrable insulin receptor antibodies in the patient's serum. DISCUSSION: Severe type B insulin resistance may respond favorably to treatment with plasmapheresis and cyclophosphamide followed by cyclosporin A in combination with azathioprin.
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| 3. |
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| 4. |
- Littorin, Bengt, et al.
(författare)
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Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment : A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes
- 1999
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 22:3, s. 409-412
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes.RESEARCH DESIGN AND METHODS:The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay.RESULTS:Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone.CONCLUSIONS:Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.
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| 5. |
- Yu, Z W, et al.
(författare)
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Cryptic receptors for insulin-like growth factor II in the plasma membrane of rat adipocytes : a possible link to cellular insulin resistance
- 1996
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 1282:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- To further elucidate the mechanisms for short-term regulation of the receptor for insulin-like growth factor II (IGF-II), we investigated effects of insulin, cAMP and phosphatase inhibitors on cell surface 125I-IGF-II binding in rat adipocytes. Preincubation with the serine/threonine phosphatase inhibitor okadaic acid (OA, 1 microM) or the non-hydrolysable cAMP analogue N6-mbcAMP (4 mM) markedly impaired insulin-stimulated 125I-IGF-II binding. Furthermore, addition of OA enhanced the inhibitory effect exerted by N6-mbcAMP. N6-mbcAMP also induced an insensitivity to insulin which was normalized by concomitant addition of the tyrosine phosphatase inhibitor vanadate (0.5 mM). In contrast, vanadate did not affect the impairment in maximal insulin-stimulated 125I-IGF-II binding produced by either OA or N6-mbcAMP. Phospholipase C (PLC), which cleaves phospholipids at the cell surface, markedly enhanced cell surface 125I-IGF-II binding in a concentration-dependent manner. Scatchard analysis demonstrated that the effect of PLC was due to an increased number of binding sites suggesting that "cryptic' IGF-II receptors are associated with the plasma membrane (PM). PLC (5 U/ml) also reversed the N6-mbcAMP-induced decrease of 125I-IGF-II binding at a low insulin concentration (10 microU/ml). Taken together, these data indicate that cAMP, similar to its effects on the glucose transporter GLUT 4 and the insulin receptor, may increase the proportion of functionally cryptic IGF-II receptors in the PM through mechanisms involving serine phosphorylation, possibly of a docking or coupling protein. Tyrosine phosphorylation appears to exert an opposite effect promoting the full cell surface expression of receptors.
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| 6. |
- Yu, Z W, et al.
(författare)
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Effects of peroxovanadate and vanadate on insulin binding, degradation and sensitivity in rat adipocytes
- 1996
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 1310:1, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- The effects of vanadate and the stable peroxovanadate compound bpV(pic) on insulin binding and degradation were investigated in rat adipocytes under conditions of ongoing receptor cycling. Both bpV(pic) and vanadate increased 125I-insulin binding to intact cells through an increase in apparent receptor affinity. The maximal effect of bpV(pic) was to increase binding approximately 4-fold (EC50 0.06 +/- 0.01 mM), whereas vanadate increased binding approximately 2-fold (EC50 1.4 +/- 0.2 mM). Removal of cell surface insulin-receptor complexes with trypsin showed that the effects on binding exerted by bpV(pic) and vanadate were due to a similar increase in both cell surface binding and intracellular accumulation of radioactivity. Both bpV(pic) and vanadate inhibited the degradation of 125I-insulin in medium containing 1% bovine serum albumin. The ratio of degraded/intact intracellular 125I-insulin was also markedly reduced by these agents, suggesting that they inhibit intracellular insulin-degrading proteases. Similar to previous findings with vanadate, bpV(pic) stimulated glucose transport and, at low concentrations, enhanced insulin sensitivity. Taken together, these data demonstrate that both bpV(pic) and vanadate inhibit insulin degradation. In addition, they significantly enhance cell surface insulin binding in rat fat cells and this is associated with an improved insulin sensitivity.
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| 7. |
- Yu, Z W, et al.
(författare)
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Peroxovanadate and insulin action in adipocytes from NIDDM patients. Evidence against a primary defect in tyrosine phosphorylation
- 1997
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 40:10, s. 1197-1203
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Tidskriftsartikel (refereegranskat)abstract
- We studied the effects of insulin and the stable peroxovanadate compound potassium bisperoxopicolinatooxovanadate (bpV(pic)), a potent inhibitor of phosphotyrosine phosphatases, on lipolysis and glucose uptake in subcutaneous adipocytes from 10 male patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 matched non-diabetic control subjects. Lipolysis stimulated by isoprenaline or the cAMP analogue, 8-bromo-cyclic AMP (8-br-cAMP), was reduced by approximately 40 % in NIDDM compared to control subjects. In both groups bpV(pic) exerted an antilipolytic effect that was similar to insulin (∼ 50 % inhibition). 14C-U-glucose uptake was dose-dependently increased by bpV(pic) treatment, but this effect and also that of insulin were impaired in NIDDM compared to control (bpV(pic) 1.6-fold vs 2.4-fold and insulin 2.2-fold vs 3.4-fold). Furthermore, low concentrations of bpV(pic) did not affect insulin-stimulated glucose uptake, although tyrosine phosphorylation of the insulin receptor β-subunit was clearly increased by bpV(pic). In conclusion, 1) β-adrenergic stimulation of lipolysis in vitro is attenuated in NIDDM adipocytes due to post-receptor mechanisms. 2) Both insulin and bpV(pic) decrease lipolysis and enhance glucose uptake in control as well as NIDDM adipocytes. The effect on glucose uptake, but not that on lipolysis, is impaired in NIDDM cells. 3) Peroxovanadate does not improve sensitivity and responsiveness to insulin in NIDDM adipocytes, showing that insulin-resistant glucose uptake in NIDDM is not overcome by phosphotyrosine-phosphatase inhibition and, thus, probably is not caused by impaired tyrosine phosphorylation events alone.
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| 8. |
- Axelsen, Mette, 1965, et al.
(författare)
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Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes.
- 1999
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Ingår i: Annals of internal medicine. - 0003-4819 .- 1539-3704. ; 131:1, s. 27-31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Impaired ability to eliminate lipids in the postprandial state is an atherogenic trait associated with insulin resistance. OBJECTIVE: To assess insulin sensitivity and postprandial triglyceride metabolism in prediabetic persons. DESIGN: Cross-sectional study. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: 13 healthy, normotriglyceridemic men with two first-degree relatives with type 2 diabetes and 13 carefully matched controls without known diabetes heredity. MEASUREMENTS: Oral glucose tolerance test, insulin sensitivity (euglycemic clamp technique), and fasting and postprandial triglyceride levels after a mixed meal. RESULTS: Relatives of persons with type 2 diabetes were insulin resistant but had normal glucose tolerance. They exhibited postprandial hypertriglyceridemia; the 6-hour triglyceride incremental area under the curve was 50% higher than that of the control group (P = 0.037). CONCLUSIONS: These healthy male first-degree relatives of patients with type 2 diabetes are insulin resistant and exhibit postprandial lipid intolerance despite having normal fasting triglyceride levels. These characteristics, which occur in the absence of glucose intolerance, are associated with an increased risk for macroangiopathy.
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| 9. |
- Dichtl, W, et al.
(författare)
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Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells
- 1999
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Ingår i: Circulation Research. - 0009-7330. ; 84:9, s. 1085-1094
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Tidskriftsartikel (refereegranskat)abstract
- High plasma levels of VLDL are associated with increased risk for atherosclerosis. Here we show that VLDL (75 to 150 microg/mL) activates nuclear factor-kappaB (NF-kappaB), a transcription factor known to play a key role in regulation of inflammation. Oxidation of VLDL reduced its capacity to activate NF-kappaB in vitro, whereas free fatty acids such as linoleic and oleic acid activated NF-kappaB to the same extent as did VLDL. Intravenous injection of human VLDL (6 mg protein per kg) into rats resulted in arterial activation of NF-kappaB as assessed by electrophoretic mobility shift assay. Aortic endothelial cells showed positive nuclear staining for the activated RelA (p65) subunit of NF-kappaB at 6 to 24 hours after injection. There was also a parallel expression of the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, as well as the cytokine tumor necrosis factor-alpha. Pretreatment of the rats with diet containing 1% of the antioxidant probucol for 8 weeks did not inhibit arterial activation of NF-kappaB in response to injection of VLDL. Moreover, injection of triglycerides (10% Intralipid, 5 mL/kg) activated arterial expression of NF-kappaB to the same extent as VLDL. Our results suggest that VLDL may promote the development of atherosclerotic lesions by activation of the proinflammatory transcription factor NF-kappaB. The effect appears to be mediated by a release of VLDL fatty acids but not to involve VLDL oxidation.
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| 10. |
- Elvanides, H, et al.
(författare)
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[Ketoacidosis also occurs in type 2 diabetes. Important risk factors are other concomitant diseases]].
- 1999
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 96:34, s. 3529-32, 3534
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Tidskriftsartikel (refereegranskat)abstract
- Although ketoacidosis has traditionally been regarded as a complication occurring only in conjunction with type I diabetes, there have recently been reports of its occurrence in cases of type II diabetes, e.g. in Afro-American and Japanese patients. The article reports a few cases suggesting that ketoacidosis may not be a rare phenomenon even in Swedish type II diabetes patients. This severe complication is usually precipitated by the occurrence of other concomitant disease.
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