Pathogenesis of Prediabetes: Role of the Liver in Isolated Fasting Hyperglycemia and Combined Fasting and Postprandial Hyperglycemia

Basu, Rita; Barosa, Cristina; Jones, John G.; Dube, Simmi; Carter, Rickey E.; Basu, Ananda; Rizza, Robert A.

doi:10.1210/jc.2012-3056

Cited by 94 publications

(82 citation statements)

References 24 publications

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“…Hepatic GNG is a notable anaplerotic pathway because of its role in the pathology of insulin resistance and diabetes (2) and its high flux relative to other hepatic pathways (3). Except for glycerol, all other gluconeogenic substrates require anaplerosis (1).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

Satapati¹,

Kucejová²,

Duarte³

et al. 2015

Journal of Clinical Investigation

329

249

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Section: Introductionmentioning

confidence: 99%

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

Satapati¹,

Kucejová²,

Duarte³

et al. 2015

Journal of Clinical Investigation

329

249

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“…It may affect various metabolic pathways which are taking place in the liver [13] . So, in this study we compare the metamorphic changes of livers enzymes in prediabetic young adult subjects and normoglycemic subjects taken from cross-sectional survey.…”

Section: Discussionmentioning

confidence: 99%

Metamorphic Changes of Liver Enzymes in Prediabetic Young Adult Subjects

Sharma¹

2018

jmscr

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“…TA exchange explains the labeling asymmetry of plasma glucose from gluconeogenic carbon tracers and contributes to the enrichment of glucose position 5 from 2 H 2 O. The fraction of hepatic G6P that undergoes TA exchange is relatively constant and does not differ with varying degrees of insulin sensitivity, ranging from healthy subjects to highly insulin-resistant patients with established type 2 diabetes, nor with varying doses of insulin (3,4,7,9). Since the effect of TA exchange on the source of EGP depends on the contribution of glycogenolysis to EGP, its effects are proportionally highest under conditions of abnor-mally high hepatic G6P production from glycogenolysis.…”

Section: Discussionmentioning

confidence: 99%

“…We have demonstrated that TA activity occurs in healthy humans based on a higher enrichment of glucose carbon 4 over carbon 3 (i.e., 13 C3/ 13 C4 Ͻ 1.0) from [1][2][3][4][5][6][7][8][9][10][11][12][13] C]acetate (3). In this study, the asymmetric labeling of glucose from this tracer could also be explained by incomplete exchange of the label between glyceraldehyde 3-phosphate and dihydroxyacetone phosphate mediated by incomplete triose phosphate isomerase (TPI; see Fig.…”

mentioning

confidence: 80%

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Effects of transaldolase exchange on estimates of gluconeogenesis in type 2 diabetes

Rajpal

Dube

Carvalho

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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13 C]acetate during a separate visit in a subset of ND (n ϭ 7) subjects. Ratio of 13 C3/ 13 C4 obtained following either tracer was Ͻ1.0 at baseline and during clamp, indicating that TPI exchange was essentially complete and did not contribute to asymmetric glucose enrichment. Uncorrected and corrected rates of gluconeogenesis were no different (P ϭ not significant) in T2DM vs. ND both at baseline and during clamp. TA correction resulted in equivalent estimates of corrected gluconeogenesis in T2DM and ND that were ϳ25-35% lower than uncorrected gluconeogenesis both at baseline and during the clamp. The asymmetric enrichment of glucose from 13 C-gluconeogenic tracers is attributable to TA exchange and can be utilized to correct for TA exchange. In conclusion, TA exchange does not differ between T2DM and ND under fasting or hyperglycemic clamp conditions, and the 2 H2O method continues to provide an accurate estimation of gluconeogenesis. gluconeogenesis; deuterated water; transaldolase; triose phosphate isomerase AFTER AN OVERNIGHT FAST, plasma glucose is not symmetrically labeled from gluconeogenic carbon tracers such as [U-13 C] glycerol (21) and [3-14 C]lactate (25). Exchange of fructose 6-phosphate and triose phosphate mediated by transaldolase has been implicated by us (3, 7, 9) and others (12) in overestimation of rates of gluconeogenesis, utilizing the deuterated water method. In this method, glucose derived from glycogenolysis (GGL) via glucose 6-phosphate (G6P) source can become labeled in carbons 4, 5, and 6 from either a carbonlabeled gluconeogenic precursor or deuterated water independent of gluconeogenesis. This results in an overestimation of the gluconeogenic fraction and a corresponding underestimation of the glycogenolytic contribution to endogenous glucose production. This exchange is particularly important in the study of type 2 diabetes mellitus (T2DM) since it mimics the characteristic shift toward increased hepatic gluconeogenic activity during the progression of this disease. With a few exceptions (14), stable isotope tracer studies indicate an increased fractional gluconeogenesis in overnight-fasted T2DM subjects compared with healthy nondiabetic (ND) controls (6,10,15,16,28). Transaldolase (TA) exchange activity has been implicated in both ND and T2DM subjects from the depletion of position 5 relative to position 3 label following metabolism of [3, H 2 ]galactose to glucose (7). However, it is not known whether transaldolase exchange activity is different between ND and T2DM under conditions of fasting and hyperglycemia (frequently seen with meals). This study was undertaken to compare TA exchange reaction in ND and T2DM subjects using [1-13 C]acetate infusion under conditions of fasting and during a hyperglycemic moderate-dose insulin clamp to determine whether or not TA exchange activity explains differences in glucose enrichment from gluconeogenic substrates between ND and T2DM subjects.We have demonstrated that TA activity occurs in healthy humans based on a higher enrichment of gluco...

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Pathogenesis of Prediabetes: Role of the Liver in Isolated Fasting Hyperglycemia and Combined Fasting and Postprandial Hyperglycemia

Cited by 94 publications

References 24 publications

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

Metamorphic Changes of Liver Enzymes in Prediabetic Young Adult Subjects

Effects of transaldolase exchange on estimates of gluconeogenesis in type 2 diabetes

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