Effect of Chronic Hyperglycemia on Glucose Metabolism in Subjects With Normal Glucose Tolerance
Article Figures & Tables
Figures
- Figure 1
Plasma glucose and insulin concentrations during the OGTT performed in NGT individuals with (FH+) and without (FH−) FH of diabetes and in the NGT control group.
- Figure 2
FPG (A), insulin (B), and FFA (C) concentrations at baseline and during 3 days of either glucose infusion in NGT individuals without (FH−, n = 10) and with (FH+, n = 10) FH of diabetes, or saline infusion in the NGT control group (n = 5). Data represent mean ± SE and were analyzed using two-way mixed-model (group × time) ANOVA. *P < 0.05, **P < 0.01, and ***P < 0.001, vs. control group and vs. baseline.
- Figure 3
Insulin-stimulated TGD (total height of bars), nonoxidative glucose disposal (NOGD) (shaded part of bars), and glucose oxidation (GOX) in FH+ and FH− individuals during the euglycemic insulin clamp performed at baseline and after 3 days of glucose infusion. Right panel shows control subjects receiving saline infusion. *P < 0.05, FH+ vs. FH−; †P < 0.05, postglucose infusion vs. baseline.
- Figure 4
Glycogen synthesis signaling. A: Skeletal muscle glycogen content at baseline and during 3 days of either glucose infusion in NGT individuals without (FH−, dark bars, n = 10) and with (FH+, white bars, n = 10) FH of diabetes, or saline infusion in the NGT control group (right panel, n = 5). Representative Western blot images of the total and phosphorylated protein expression (top panel) and densitometry quantitation of the phosphorylated-to-total ratio of GS (B) and GSK3β (C). G6P (D) and glycogen (E) concentrations in skeletal muscle of all subjects receiving glucose infusion. Data are expressed as the mean ± SE and were analyzed using two-way repeated-model (clamp × infusion) ANOVA. *P < 0.05, **P < 0.01, and ***P < 0.001, for clamp vs. basal; ^P < 0.05 and ^^^P < 0.001, postglucose infusion vs. baseline. CON, control.
- Figure 5
PDH regulation and insulin signaling. Representative Western blot images and densitometry quantitation of PDK4 protein expression (A), PDH E1α subunit phosphorylation (B), and Akt phosphorylation (D) and PDH activation status (C) at baseline (black bars) and after 3 days of glucose (white bars) infusion in NGT subjects. Data represent mean ± SE and were analyzed using two-way mixed-model (group × clamp; group × infusion) ANOVA. *P < 0.05, **P < 0.01, and ***P < 0.001 for clamp vs. basal; ^P < 0.05 and ^^^P < 0.001, postglucose infusion vs. baseline.
- Figure 6
Basal O-GlcNAcylated protein quantification before and after 3 days of saline (white bars) or glucose (black bars) infusion (A) and representative blot for three subjects receiving glucose infusion (B). Basal and insulin-stimulated OGT (C) and GFAT1 (D) quantification before (black bars) and after (white bars) 3 days of glucose infusion and representative blots (E). Data represent mean ± SE and were analyzed using two-way mixed-model (group × clamp; group × infusion) ANOVA. BL, baseline; GLU, glucose.
Tables
- Table 1
Baseline patient characteristics
FH− FH+ Control Number 10 10 5 Age (years) 45 ± 4 43 ± 5 49 ± 4 Sex (male/female) 7/3 6/4 2/3 Ethnicity (Mexican American/Caucasian/African American) 3/4/3 6/3/1 1/4 BMI (kg/m2) 24.3 ± 1.1 26.1 ± 1.2 24.5 ± 1.3 Body weight (kg) 75.6 ± 16.3 73.7 ± 10.9 72.6 ± 11.5 Fat-free mass (kg) 57.4 ± 12.8 51.5 ± 9.6 52.0 ± 11.2 HbA1c (%) 5.4 ± 0.1 5.4 ± 0.1 5.4 ± 0.1 FPG (mg/dL) 96.2 ± 2.6 100.7 ± 2.0 94.1 ± 5.2 2-h plasma glucose (mg/dL) OGTT 95 ± 5 109 ± 6 111 ± 5 Data are mean ± SD or n. There were no significant differences between the FH−, FH+, and control groups.
- Table 2
TGD, nonoxidative glucose disposal, glucose oxidation, and rEGP (primarily reflects hepatic) during the insulin clamp before and after glucose infusion
FH− FH+ Control Baseline insulin clamp Steady-state plasma glucose (mg/dL) 94.8 ± 1.8 95.9 ± 1.6 94.9 ± 3.3 Steady-state plasma insulin (µU/mL) 163 ± 2 172 ± 12 125 ± 8 bEGP (mg/kg/min) 2.33 ± 0.08 2.09 ± 0.09 2.46 ± 0.11 bEGP × basal insulin ([µU/mL] · [mg/kg/min]) 20.5 ± 1.9 19.3 ± 4.2 19.2 ± 1.7 TGD (mg/kg/min) 11.49 ± 0.91 9.32 ± 0.49* 11.18 ± 1.64 rEGP (mg/kg/min) 0.56 ± 0.2 0.56 ± 0.33 0.34 ± 0.26 Basal glucose oxidation (mg/kg/min) 1.33 ± 0.13 1.14 ± 0.18 1.34 ± 0.13 Clamp glucose oxidation (mg/kg/min) 2.75 ± 0.53 1.81 ± 0.26* 2.45 ± 0.17 Nonoxidative glucose disposal (mg/kg/min) 8.69 ± 0.82 7.46 ± 0.61 8.35 ± 1.88 Basal LOX (mg/kg/min) 0.92 ± 0.10 0.94 ± 0.09 0.99 ± 0.19 Clamp LOX (mg/kg/min) 0.50 ± 0.08 0.74 ± 0.11 0.45 ± 0.2 Basal RER 0.81 ± 0.02 0.80 ± 0.02 0.81 ± 0.02 Clamp RER 0.90 ± 0.02 0.85 ± 0.02 0.91 ± 0.03 Insulin clamp post–glucose infusion Steady-state plasma glucose (mg/dL) 96.1 ± 2.0 98.1 ± 1.4 96.9 ± 2.0 Steady-state plasma insulin (µU/mL) 208 ± 24 198 ± 10 121 ± 8 bEGP (mg/kg/min) 3.87 ± 0.37†† 3.63 ± 0.27†† 2.27 ± 0.11 bEGP × basal insulin ([µU/mL] ⋅ [mg/kg/min]) 74.9 ± 12.8†† 59.1 ± 5.5††† 20.4 ± 1.0 TGD (mg/kg/min) 9.46 ± 0.69††† 8.12 ± 0.55†† 10.65 ± 1.61 rEGP (mg/kg/min) 0.54 ± 0.22 0.47 ± 0.11 0.14 ± 0.09 Basal glucose oxidation (mg/kg/min) 4.64 ± 0.39 3.78 ± 0.25 1.35 ± 0.18 Clamp glucose oxidation (mg/kg/min) 5.12 ± 0.37† 4.39 ± 0.29† 3.03 ± 0.21 Nonoxidative glucose disposal (mg/kg/min) 4.28 ± 0.60† 4.11 ± 0.69† 7.61 ± 1.69 Basal LOX (mg/kg/min) −0.14 ± 0.12 0.14 ± 0.06 0.86 ± 0.04 Clamp LOX (mg/kg/min) −0.15 ± 0.12 0.09 ± 0.08 0.42 ± 0.11 Basal RER 1.0 ± 0.02 0.97 ± 0.01 0.81 ± 0.01 Clamp RER 1.0 ± 0.02 0.98 ± 0.01 0.92 ± 0.01 Data are mean ± SE. LOX, lipid oxidation.
*P < 0.05, FH+ vs. FH−.
†P < 0.001, post–glucose infusion vs. baseline.
††P = 0.08, post–glucose infusion vs. baseline.
†††P = 0.02, post–glucose infusion vs. baseline.
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