Intramuscular triglyceride and muscle insulin sensitivity: Evidence for a relationship in nondiabetic subjects

Phillips, David I. W.; Caddy, Sarah; Ilic, Vera; Fielding, Barbara A.; Frayn, Keith N.; Borthwick, A C; Taylor, Richard D.

doi:10.1016/s0026-0495(96)90260-7

Cited by 352 publications

(266 citation statements)

References 23 publications

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“…IMTG is best correlated with an individual's degree of insulin resistance, regardless of BMI [6][7][8]. No differences in IMTG were observed in LGI or HGI, indicating that hyperglycaemia-hyperinsulinaemia is not sufficient to elicit higher levels of IMTG in myotubes of post-diabetes mellitus participants.…”

Section: Discussionmentioning

confidence: 89%

“…The molecular mechanisms responsible for the progression of insulin resistance are still poorly understood. Ectopic accumulation of lipid in skeletal muscle (intramuscular triacylglycerol [IMTG]) is associated with obesity and highly correlated with the development of insulin resistance [6][7][8]. However, the observation that lean, insulin-sensitive endurance-trained athletes have high levels of IMTG has led to the hypothesis that altered or incomplete lipid metabolism may be an important factor in the progression of insulin resistance (reviewed by van Loon and Goodpaster [9]).…”

Section: Introductionmentioning

confidence: 99%

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Increased susceptibility to oxidative damage in post-diabetic human myotubes

et al. 2009

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Aims/hypothesis Obesity is an important risk factor for the development of type 2 diabetes, but not all obese individuals develop this complication. The clinical signs of type 2 diabetes can often be reversed with weight loss; however, it is unknown whether the skeletal muscle oxidative stress associated with type 2 diabetes remains after weight loss. We hypothesised that chronic exposure to high glucose and insulin would re-elicit impaired metabolism in primary myotubes from patients with a history of type 2 diabetes. Methods Obese participants with or without type 2 diabetes completed a standardised weight loss protocol, following which all participants were euglycaemic and had similar indices of insulin sensitivity. Satellite cells were isolated from muscle biopsies and differentiated under low or high glucose and insulin conditions (HGI).

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Increased susceptibility to oxidative damage in post-diabetic human myotubes

et al. 2009

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“…The expression levels were calculated and expressed as the mean ratio to β-actin expression ± SEM. n=5 and n=4 for transgenic and control rabbits respectively though we cannot exclude the possibility that transgenic rabbits may have (locally) hepatic insulin resistance associated with the fatty liver [30,31,32], overall effect of LPL overexpression on insulin sensitivity was apparently beneficial. These findings in transgenic rabbits contrast with the results in transgenic mice that showed insulin resistance accompanied by accumulation of TG in their skeletal muscle [16] or liver [4].…”

Section: Discussionmentioning

confidence: 96%

Overexpression of lipoprotein lipase improves insulin resistance induced by a high-fat diet in transgenic rabbits

Kitajima¹,

Morimoto²,

Liu³

et al. 2004

Diabetologia

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Aims/hypothesis. Dysfunctions of lipoprotein lipase (LPL) have been found to be associated with dyslipidaemias, atherosclerosis, obesity and insulin resistance. There are two conflicting hypotheses regarding the roles of LPL in glucose metabolism and insulin resistance. Whether systemically increased LPL activity would be beneficial or detrimental to insulin sensitivity is yet to be resolved. To address this issue, we studied transgenic rabbits overexpressing human LPL transgene. Methods. LPL transgenic and control rabbits were fed a 10% high-fat diet (HFD) for 16 weeks. To evaluate glucose metabolism, we compared plasma levels of glucose and insulin in transgenic rabbits with control rabbits and performed an intravenous glucose tolerance test. In addition, we measured adipose tissue accumulation in HFD-fed rabbits.Results. Increased LPL activity in transgenic rabbits resulted in a significant reduction of plasma triglycerides and non-esterified fatty acids, but not in basal levels of glucose and insulin. HFD feeding induced an elevation of plasma glucose levels accompanied by hyperinsulinaemia in control rabbits, but was significantly inhibited in transgenic rabbits. The intravenous glucose tolerance test showed that transgenic rabbits had faster glucose clearance associated with lower levels of insulin secretion than control rabbits. In addition, there was a significant reduction of body adipose tissue in transgenic rabbits compared with in control rabbits fed an HFD. Scanning electron microscopic examination revealed that adipocytes in transgenic rabbits were predominately small cells. Conclusions/interpretation. Our results showed that systemically increased LPL activity improves insulin resistance and reduces adipose accumulation in transgenic rabbits, indicating that systemic elevation of LPL may have potential benefits for the treatment of insulin resistance and obesity.

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“…Furthermore, a combined excess in energy intake and impaired adipogenesis could be manifested as enlarged fat cells and NEFA spill-over from adipose tissue to muscle and liver, where they accumulate as ectopic triacylglycerols. This is found in obese subjects and subjects with type 2 diabetes [10,42] and is associated with reduced insulin sensitivity [43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’

et al. 2007

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Aims/hypothesis The aim of this study was to explore whether fat cell size in human subcutaneous and omental adipose tissue is independently related to insulin action and adipokine levels. Materials and methods Fat cells were prepared from abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non-diabetic subjects and from omental biopsies obtained from 37 non-diabetic subjects. Cell size and insulin action on glucose uptake capacity in vitro were assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and adipokines and NEFA were measured. Results Negative correlations were found between subcutaneous fat cell size and insulin sensitivity assessed as M-value during clamp and as insulin action on glucose uptake in fat cells in vitro. This was seen in non-diabetic subjects after including age, sex and BMI in the analyses. No such relationship was found in type 2 diabetic subjects. In both groups, subcutaneous fat cell size correlated positively and independently with plasma levels of leptin but not to any of the other assessed adipokines. In nondiabetic subjects, omental fat cell size was independently and negatively correlated with insulin action in subcutaneous, but not omental, fat cells in vitro.Conclusions/interpretation Fat cell enlargement is associated with insulin resistance in non-diabetic individuals independently of BMI. This was not seen in type 2 diabetic subjects, suggesting that after development of type 2 diabetes other factors, not related to fat cell size, become more important for the modulation of insulin resistance.

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Intramuscular triglyceride and muscle insulin sensitivity: Evidence for a relationship in nondiabetic subjects

Cited by 352 publications

References 23 publications

Increased susceptibility to oxidative damage in post-diabetic human myotubes

Increased susceptibility to oxidative damage in post-diabetic human myotubes

Overexpression of lipoprotein lipase improves insulin resistance induced by a high-fat diet in transgenic rabbits

Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’

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