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- Title
Interaction of High Fat Feeding and Impaired Glucose Phosphorylation Capacity in Control of Muscle Glucose Uptake during Insulin Stimulation and Exercise.
- Authors
Fueger, Patrick T.; Lee-Young, Robert S.; Shearer, Jane; Bracy, Deanna P.; Heikkinen, Sami; Laakso, Markku; Wasserman, David H.
- Abstract
Muscle glucose uptake (MGU) is regulated by glucose delivery to, transport into, and phosphorylation within muscle. The aim of this study was to determine the role of limitations in glucose phosphorylation in control of MGU during exercise and insulin stimulation with chow (CH) or high fat (HF) feeding. C57BL/6J mice with (HK[sup +/-]) and without (WT) a partial hexokinase II deletion were fed CH or HF diets and studied at 4 mo of age during a 120 min insulin clamp or 30 min of treadmill exercise (n = 8-10 mice/group). 2-deoxy[³H]glucose was used to measure R[sub g], an index of MGU. Body weight and fasting arterial glucose were increased by HF feeding but not HK[sup +/-] (26±1, 35±1,25±1, and 35±1 g; 169±4, 195±4, 174±5, and 190±8 mg/dL for CH-WT, HF-WT, CH-HJ[sup +/-] and HF-HK[sup +/-]). Both HF feeding and HK[sup +/-] independently created fasting hyperinsulinemia and this response was increased synergistically with combined HF feeding and HK[sup +/-] (22±2, 60±8, 35±3, and 113±13 µU/mL for CH-WT, HF-WT, CH-HK[sup +/-], and HF-HK[sup +/-]). Whole-body insulin sensitivity (as measured by the glucose infusion during the clamps) was suppressed by 20 to 30% in HF feeding and HK[sup +/-] but by over 50% when the two were combined (59±5, 41±5, 47±4 and 28±4 mg/kg/min for CH-WT, HF-WT, CH-HK[sup +/-], and HF-HK[sup +/-]). In addition, insulin-stimulated R[sub g] was modestly impaired by HF feeding and HK[sup +/-], independently, while combination of the two markedly reduced R[sub g] (100±12, 81±12, 88±12, and 56±13% of rates seen in CH-WT for CH-WT, HF-WT, CH-HK[sup +/-], and HF-HK[sup +/-]). In contrast, during exercise, R[sub g] was equally reduced by HF feeding, HK[sup +/-] alone, and by the combination of the two (100±19, 49±13, 52±9, and 49±10% for CH-WT, HF-WT, CH-HK[sup +/-], and HF-HK[sup +/-]). In summary, the impairments in whole body metabolism and MGU during insulin stimulation due to HF feeding and HK[sup +/-] combined are additive suggesting that dietary insulin resistance in the mouse is not limited by glucose phosphorylation capacity, but by muscle glucose delivery or transport. In contrast, combining HF feeding and HK[sup +/-] during exercise causes no greater impairment in MGU. This suggests that MGU is impaired by HF feeding due, in large part, to a limitation in glucose phosphorylation capacity. These studies reveal that the high fat fed mouse is characterized by defects at multiple steps of the MGU system.
- Subjects
FAT content of food; GLUCOSE; PHOSPHORYLATION; INSULIN; EXERCISE; LABORATORY mice
- Publication
Diabetes, 2007, Vol 56, pA401
- ISSN
0012-1797
- Publication type
Article