Interactions among glucose delivery, transport, and phosphorylation that underlie skeletal muscle insulin resistance in obesity and type 2 diabetes: Studies with dynamic pet imaging

Bret H. Goodpaster, Alessandra Bertoldo, Jason M. Ng, Koichiro Azuma, R. Richard Pencek, Carol Kelley, Julie C. Price, Claudio Cobelli, David E. Kelley

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Dynamic positron emission tomography (PET) imaging was performed using sequential tracer injections ([15O]H2O, [ 11C]3-O-methylglucose [3-OMG], and [18F]fluorodeoxyglucose [FDG]) to quantify, respectively, skeletal muscle tissue perfusion (glucose delivery), kinetics of bidirectional glucose transport, and glucose phosphorylation to interrogate the individual contribution and interaction among these steps in muscle insulin resistance (IR) in type 2 diabetes (T2D). PET imaging was performed in normal weight nondiabetic subjects (NW) (n = 5), obese nondiabetic subjects (OB) (n = 6), and obese subjects with T2D (n = 7) during fasting conditions and separately during a 6-h euglycemic insulin infusion at 40 mU -2 min -1. Tissue tracer activities were derived specifically within the soleus muscle with PET images and magnetic resonance imaging. During fasting, NW, OB, and T2D subjects had similar [11C]3-OMG and [18F]FDG uptake despite group differences for tissue perfusion. During insulin-stimulated conditions, IR was clearly evident in T2D (P < 0.01), and [18F]FDG uptake by muscle was inversely correlated with systemic IR (P < 0.001). The increase in insulin-stimulated glucose transport was less (P < 0.01) in T2D (twofold) than in NW (sevenfold) or OB (sixfold) subjects. The fractional phosphorylation of [18F]FDG during insulin infusion was also significantly lower in T2D (P < 0.01). Dynamic triple-tracer PET imaging indicates that skeletal muscle IR in T2D involves a severe impairment of glucose transport and additional impairment in the efficiency of glucose phosphorylation.

Original languageEnglish
Pages (from-to)1058-1068
Number of pages11
JournalDiabetes
Volume63
Issue number3
DOIs
Publication statusPublished - 2014 Mar
Externally publishedYes

Fingerprint

Pets
Type 2 Diabetes Mellitus
Insulin Resistance
Skeletal Muscle
Obesity
Phosphorylation
Glucose
Fluorodeoxyglucose F18
Positron-Emission Tomography
3-O-Methylglucose
Insulin
Muscles
Fasting
Perfusion
Magnetic Resonance Imaging
Weights and Measures
Injections

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Interactions among glucose delivery, transport, and phosphorylation that underlie skeletal muscle insulin resistance in obesity and type 2 diabetes : Studies with dynamic pet imaging. / Goodpaster, Bret H.; Bertoldo, Alessandra; Ng, Jason M.; Azuma, Koichiro; Pencek, R. Richard; Kelley, Carol; Price, Julie C.; Cobelli, Claudio; Kelley, David E.

In: Diabetes, Vol. 63, No. 3, 03.2014, p. 1058-1068.

Research output: Contribution to journalArticle

Goodpaster, BH, Bertoldo, A, Ng, JM, Azuma, K, Pencek, RR, Kelley, C, Price, JC, Cobelli, C & Kelley, DE 2014, 'Interactions among glucose delivery, transport, and phosphorylation that underlie skeletal muscle insulin resistance in obesity and type 2 diabetes: Studies with dynamic pet imaging', Diabetes, vol. 63, no. 3, pp. 1058-1068. https://doi.org/10.2337/db13-1249
Goodpaster, Bret H. ; Bertoldo, Alessandra ; Ng, Jason M. ; Azuma, Koichiro ; Pencek, R. Richard ; Kelley, Carol ; Price, Julie C. ; Cobelli, Claudio ; Kelley, David E. / Interactions among glucose delivery, transport, and phosphorylation that underlie skeletal muscle insulin resistance in obesity and type 2 diabetes : Studies with dynamic pet imaging. In: Diabetes. 2014 ; Vol. 63, No. 3. pp. 1058-1068.
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