Defects in beta-cell function and insulin sensitivity in normoglycemic @entity3839 -treated XXXX : a model of @entity1723 .

@entity1 @entity44717 @entity3839 @entity1723 @entity6599 @entity369 @entity4854 @entity413
During the preclinical period of @entity1 @entity1723 , both impaired pancreatic beta-cell function and increased insulin resistance are found, although normoglycemia is preserved. To better understand the changes in beta-cell function and insulin sensitivity that occur in @entity1723 , we performed a panel of in vivo beta-cell function tests and measured insulin sensitivity in adolescent male @entity6599 both in normal health and after a small dose of @entity3839 which did not induce @entity4854 . Nine animals were studied before (stage 1) and 1 week after receiving a low dose of @entity3839 (stage 2). There was no change in fasting plasma @entity413 or insulin. The mean @entity413 disposal rate (Kg) remained within the normal range, but dropped from 2.0 +/- 0.2% +/- SE) to 1.2 +/- 0.1%/min (P less than 0.01), the acute insulin response to @entity369 (AIR(arg)) fell from 67.7 +/- 19.4 microU/mL (485.8 +/- 139.2 pmol/L) to 32.8 +/- 7.2 microU/mL (235.3 +/- 51.7 pmol/L; P less than 0.05), and the acute insulin response to @entity413 (AIR(gluc)) fell from 881 +/- 243 microU/mL.10 min (6321 +/- 1744 pmol/L.10 min) to 334 +/- 82 microU/mL.10 min (2396 +/- 588 pmol/L.10 min; P less than 0.01). The most dramatic change, however, was in the ability of @entity4854 to potentiate AIR(arg) (expressed as the slope of potentiation). This was reduced by 94% from 1.8 +/- 0.5 to 0.1 +/- 0.1 (P less than 0.01), with almost no overlap in values between stages 1 and 2. Insulin sensitivity was also lower 1 week after @entity3839 treatment. When the animals were restudied 8 weeks after @entity3839 treatment (stage 3) most measures of beta-cell function were not significantly different from those in stage 1. The fasting plasma @entity413 level was 85.4 +/- 4.3 mg/ @entity44717 +/- 0.2 mmol/L), Kg was 1.8 +/- 0.3%/min, fasting plasma insulin was 35.9 +/- 8.5 microU/mL (257.6 +/- 61.0 pmol/L), AIR(arg) was 67.0 +/- 15.4 microU/mL (480.7 +/- 110.5 pmol/L), and AIR(gluc) was 615.3 +/- 265.3 microU/mL.10 min (4413 +/- 1901 pmol/L.10 min), and tissue insulin sensitivity was 2.7 +/- 0.4 x 10(4) min/microU.mL. These values show extensive overlap with those of stage 1, from which they are not significantly different. The slope of @entity413 potentiation, however, remained low in all animals at stage 3.(ABSTRACT TRUNCATED AT 400 WORDS)
