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The Relationship between Plasma Triglyceride and Hepatic Insulin Resistance and Effects of Fatty Acids on Hepatic Glucose Uptake

Author: WangPing
Tutor: MuYiMing
School: PLA Postgraduate Medical School
Course: Internal Medicine
Keywords: Palmitic acid Arachidonic acid Glucose uptake Insulin receptor Glucose transporter 2 Hypertriglyceridemia Insulin-like growth factor binding protein-1 Insulin resistance
CLC: R589.2
Type: Master's thesis
Year: 2005
Downloads: 184
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Abstract

1. Serum levels of IGFBP-1 and their relationships to insulin sensitivity in type 2 diabetes and hypertriglyceridemiaObjective To observe serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations in normal subjects and subjects with type 2 diabetes mellitus (T2DM) or hypertriglyceridemia, and to evaluate their possible relationships to age, sex, body mass, fat distribution, metabolic and hormonal variables, and to assess the effects of hypertriglyceridemia on hepatic insulin sensitivity and insulin-like growth factors system.Subjects and Methods Sixty six subjects (38 males and 28 females, mean age 50.33±10.62) were recruited, among which there were 15 subjects with T2DM without hypertriglyceridemia (8 males and 7 females), 21 subjects with both T2DM and hypertriglyceridemia (15 males and 6 females), 15 subjects with hypertriglyceridemia without T2DM (9 males and 6 females), 15 normal subjects (8 males and 7 females). IGFBP-1 was measured by ELISA. Body mass index (BMI), waist hip ratio (WHR), fasting plasma glucose (FPG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), lower density lipoprotein (LDL) levels and Homa-IR (Homa-IR=FINSx FPG/22.5) were measured in all subjects.Results 1. Comparing with the control (3.36±0.29 ng/ml), serumlevels of IGFBP-1 significantly decreased in the group with hypertriglyceridemia (2.37±0.46 ng/ml) (P<0.05). The subjects with both T2DM and hypertriglyceridemia had lower levels of IGFBP-1 (3.01±0.47 ng/ml) than subjects with T2DM without hypertriglyceridemia (3.45±0.37 ng/ml) (P<0.05), but serum IGFBP-1 levels showed no significant difference between diabetic group and the control (P>0.05); 2. Serum IGFBP-1 level was negatively correlated with BMI (r=-0.573, P=0.000), TG (r=-0.387, P=0.002), FINS (r=-0.485, P=0.000), Homa-IR (r=-0.306, P=0.016), and positively correlated with HDL (r=0.431, P=0.001). Age, WHR, HbA1c, TC, LDL, FPG were independent factors for serum IGFBP-1 level (P>0.05).Conclusions Serum IGFBP-1 levels significantly decreased in subjects with hypertriglyceridemia. Serum IGFBP-1 was significantly correlated with plasma TG, fat distribution and insulin resistance and it could well reflect hepatic insulin resistance status. There was significant hepatic insulin resistance in hypertriglyceridemia. Hypertriglyceridemia was one of the causes of hepatic insulin resistance and plasma TG had more significant effect on hepatic insulin resistance than plasma glucose.2. Effects of palmitic acid and arachidonic acid on the glucose uptake in HepG2 cells and the possible mechanismObjective To observe the effects of saturated fatty acids (SFAs) -palmitic acid (PA) and polyunsaturated fatty acids (PUFAs) - arachidonic acid (AA) on glucose uptake in HepG2 cells and the possible mechanism.Methods After the HepG2 cells incubated with different concentrations of PA or AA for 24 hours, the uptake of 2-deoxy-[~3H]-D-glucose was measured. The levels of insulin receptor (InsR)and glucose transporter 2 (GLuT2) mRNAs were determined by RT-PCR. Western blotting was used to assess the levels of InsR and GLuT2 proteins.Results 1. PA, at concentrations of 100 and 200 umol/L, increased the glucose uptake of HepG2 cells to 145% and 132% of the control group respectively (both P values <0.01). While at concentrations of 400 and 600 umol/L, PA significantly reduced the glucose uptake to 72% and 37% of the control group respectively (both P values <0.01); 2. AA, at concentrations of 5-15 umol/L, could increase the glucose uptake of HepG2 cells, especially at 10 umol/L which increased the glucose uptake to 129% of the control (PO.01). Furthermore, when incubated the HepG2 cells with both 10 umol/L AA and different concentrations of PA, the glucose uptake of HepG2 cells showed no significant change in PA exposure at concentrations of 100 or 200 umol/L; but at 400 and 600 umol/L of PA, the glucose uptake increased from 72% and 37% to 99% and 83% of the control group respectively (both P values <0.01); 3. PA, at 100 and 200 umol/L, could stimulated the expressions of the mRNAs and proteins of InsR and GLuT2 in the HepG2 cells, but 400 umol/L of PA could significantly inhibit the expressions of the mRNAs and proteins of InsR and GLuT2. At the concentration of 10 umol/L, AA could also stimulate the expressions of the mRNAs and proteins of InsR and GLuT2. When incubated the HepG2 cells with both 10 |imol/L AA and different concentrations of PA, the levels of mRNAs and proteins of InsR and GLuT2 showed no significant change in PA exposure at concentrations of 100 or 200 umol/L, but AA could partly prevent the decrease of the levels of mRNAs and proteins of InsR and GLuT2 induced by 400 umol/L of PA.Conclusions Decrease of InsR and GLuT2 protein and mRNA abundance might contribute to the insulin resistance induced by SFAs of high concentrations. AA could increase the glucose uptake of HepG2 cells through stimulating the expressions of InsR and GluT2, which could also

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