Role of insulin resistance in the pathogenesis of NIDDM

Yki‐Järvinen, Hannele

doi:10.1007/bf00400597

Cited by 115 publications

(83 citation statements)

References 135 publications

(103 reference statements)

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“…However, at this stage, it is not possible to be sure who is a true prediabetic. Moreover, in these studies it is important to properly match experimental and control groups for acquired variables (e.g., obesity, age, physical fitness) which affect ß-cell function and insulin sensitivity (9). Finally, the findings for a specific ethnic group, such as the Pima Indians, the Nauruans, the Mexican-or African-Americans may be not valid for other type 2 diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

Pimenta

Santos

Cruz

et al. 2003

Braz J Med Biol Res

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To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH-individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) µU/ml, and c) ISI,.0) mg kg -1 min -1 /µU ml -1 . Hepatic insulin extraction in FH+ subjects was similar to that of FH-ones at basal conditions (median, 0.27 vs 0.27 ng/µU) and during glucose infusion (0.15 vs 0.15 ng/µU). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH-ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

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Section: Introductionmentioning

confidence: 99%

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

Pimenta

Santos

Cruz

et al. 2003

Braz J Med Biol Res

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“…Transdermal estradiol replacement therapy in estrogen-deficient postmenopausal women was shown to improve b-cell function in vivo and to augment insulin secretion in response to an acute glucose challenge (11,12).…”

Section: Introductionmentioning

confidence: 99%

Effect of estradiol on insulin secreting INS-1 cells overexpressing estrogen receptors

Horn

Möhlig²,

Osterhoff³

et al. 2000

European Journal of Endocrinology

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Background: Estrogen has been shown to have profound effects on insulin and glucose metabolism in vivo. Indeed, estrogens were recently shown to modulate ion channel and secretory activities in endocrine cells. Design and Methods: To investigate whether estrogenic influences are caused by direct effects on pancreatic b-cells, we equipped INS-1 insulinoma cells with estrogen receptors and monitored insulin content and Ca 2+ fluxes as well as basal and stimulated insulin secretion upon different stimuli including glucose, the Ca 2+ ionophore ionomycin, the Ca 2+ channel agonist BayK8644, the protein kinase C activator TPA, and the adenylate cyclase activator forskolin. Results and Conclusion: Our data reveal that estradiol has no significant direct effect on proliferation rate, insulin content, basal and stimulated insulin output as well as Ca 2+ fluxes of insulin secreting cells in vitro, indicating that in vivo responses to estrogen on insulin and glucose metabolism result from indirect betacytotropic effects.

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“…We identified 14 pairs of initially NGT individuals, one progressor and 1 non-progressor, matched for main insulin resistance determining factors (15). Even though the progressor group had a significantly higher W/H ratio than the non-progressor group, the W/H ratio for the progressor group was only a little above normal.…”

Section: Comparative Analysis Of Initial Demographic and Metabolic Chmentioning

confidence: 99%

Demographic and metabolic characteristics of individuals with progressive glucose tolerance

Mendes

Santos

Padovani

et al. 2009

Braz J Med Biol Res

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We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT) were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT), insulin secretion (first and second phases) and insulin sensitivity indices (from hyperglycemic clamp assay) for both groups. In the normal glucose tolerant phase, progressors presented: 1) a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2) a reduced first-phase insulin secretion (2.0 ± 0.3 vs 2.3 ± 0.3 pmol/L; P < 0.02) with a similar insulin sensitivity index and a lower disposition index (3.9 ± 0.2 vs 4.1 ± 0.2 μmol·kg -1 ·min -1 ; P < 0.05) vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05) and reduced early insulin response to OGTT (progressors, 1st: 2.10 ± 0.34 vs 2nd: 1.87 ± 0.25 pmol/mmol; non-progressors, 1st: 2.15 ± 0.28 vs 2nd: 2.03 ± 0.39 pmol/mmol; P < 0.05). Theses data suggest that β-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

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Role of insulin resistance in the pathogenesis of NIDDM

Cited by 115 publications

References 135 publications

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

Effect of estradiol on insulin secreting INS-1 cells overexpressing estrogen receptors

Demographic and metabolic characteristics of individuals with progressive glucose tolerance

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