Morphometric documentation of abnormal intramyocellular fat storage and reduced glycogen in obese patients with Type II diabetes

Levin, Klaus; Schroeder, Henrik Daa; Alford, F. P.; Beck‐Nielsen, Henning

doi:10.1007/s001250100545

Cited by 95 publications

(10 citation statements)

References 33 publications

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“…We first showed that the patients with type 2 diabetes (and thus insulin resistance) had increased accumulation of lipid droplets in their skeletal muscle, in agreement with earlier results (1,17,18). There was very little lipid accumulation in biopsy samples from both lean healthy and obese nondiabetic control subjects, demonstrating that obese people do not necessarily store fat in their skeletal muscles.…”

Section: Discussionsupporting

confidence: 91%

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The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes

et al. 2010

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OBJECTIVEOur previous studies suggest that the SNARE protein synaptosomal-associated protein of 23 kDa (SNAP23) is involved in the link between increased lipid levels and insulin resistance in cardiomyocytes. The objective was to determine whether SNAP23 may also be involved in the known association between lipid accumulation in skeletal muscle and insulin resistance/type 2 diabetes in humans, as well as to identify a potential regulator of SNAP23.RESEARCH DESIGN AND METHODSWe analyzed skeletal muscle biopsies from patients with type 2 diabetes and healthy, insulin-sensitive control subjects for expression (mRNA and protein) and intracellular localization (subcellular fractionation and immunohistochemistry) of SNAP23, and for expression of proteins known to interact with SNARE proteins. Insulin resistance was determined by a euglycemic hyperinsulinemic clamp. Potential mechanisms for regulation of SNAP23 were also investigated in the skeletal muscle cell line L6.RESULTSWe showed increased SNAP23 levels in skeletal muscle from patients with type 2 diabetes compared with that from lean control subjects. Moreover, SNAP23 was redistributed from the plasma membrane to the microsomal/cytosolic compartment in the patients with the type 2 diabetes. Expression of the SNARE-interacting protein Munc18c was higher in skeletal muscle from patients with type 2 diabetes. Studies in L6 cells showed that Munc18c promoted the expression of SNAP23.CONCLUSIONSWe have translated our previous in vitro results into humans by showing that there is a change in the distribution of SNAP23 to the interior of the cell in skeletal muscle from patients with type 2 diabetes. We also showed that Munc18c is a potential regulator of SNAP23.

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Section: Discussionsupporting

confidence: 91%

“…Insulin resistance plays a major role in the development of type 2 diabetes and is highly related to the accumulation of triglycerides in skeletal muscle (1,2). Triglycerides are stored in the cell in cytosolic lipid droplets, which consist of a core of neutral lipids surrounded by a monolayer of amphipathic lipids (3,4).…”

mentioning

confidence: 99%

The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes

et al. 2010

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“…In spite of their IR and reduced cardiovascular fitness, T1D youth showed paradoxically normal intramyocellular lipid content (IMCL). This finding contradicts the previously well- established theory that IMCL accumulation is a marker for insulin resistance in both T1D and T2D [39], [40].…”

Section: Discussioncontrasting

confidence: 99%

Metabolomics Approach for Analyzing the Effects of Exercise in Subjects with Type 1 Diabetes Mellitus

et al. 2012

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The beneficial effects of exercise in patients with type 1 diabetes (T1D) are not fully proven, given that it may occasionally induce acute metabolic disturbances. Indeed, the metabolic disturbances associated with sustained exercise may lead to worsening control unless great care is taken to adjust carbohydrate intake and insulin dosage. In this work, pre- and post-exercise metabolites were analyzed using a 1H-NMR and GC-MS untargeted metabolomics approach assayed in serum. We studied ten men with T1D and eleven controls matched for age, body mass index, body fat composition, and cardiorespiratory capacity, participated in the study. The participants performed 30 minutes of exercise on a cycle-ergometer at 80% VO2max. In response to exercise, both groups had increased concentrations of gluconeogenic precursors (alanine and lactate) and tricarboxylic acid cycle intermediates (citrate, malate, fumarate and succinate). The T1D group, however, showed attenuation in the response of these metabolites to exercise. Conversely to T1D, the control group also presented increases in α-ketoglutarate, alpha-ketoisocaproic acid, and lipolysis products (glycerol and oleic and linoleic acids), as well as a reduction in branched chain amino acids (valine and leucine) determinations. The T1D patients presented a blunted metabolic response to acute exercise as compared to controls. This attenuated response may interfere in the healthy performance or fitness of T1D patients, something that further studies should elucidate.

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“…LD accumulation in skeletal muscle is closely linked to insulin resistance (e.g., Refs. 15,16,27,37), and recent studies suggest that an accumulation of LDs specifically in the subsarcolemmal location is detrimental for insulin sensitivity compared with LDs in the intermyofibrillar location (3, 9, 28, 35). However, the underlying mechanism remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Lipid droplet size and location in human skeletal muscle fibers are associated with insulin sensitivity

Nielsen

Christensen

Nellemann

et al. 2017

American Journal of Physiology-Endocrinology and Metabolism

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In skeletal muscle, an accumulation of lipid droplets (LDs) in the subsarcolemmal space is associated with insulin resistance, but the underlying mechanism is not clear. We aimed to investigate how the size, number, and location of LDs are associated with insulin sensitivity and muscle fiber types and are regulated by aerobic training and treatment with an erythropoiesis-stimulating agent (ESA) in healthy young untrained men. LD analyses were performed by quantitative transmission electron microscopy, and insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp. At baseline, we found that only the diameter (and not the number) of individual subsarcolemmal LDs was negatively associated with insulin sensitivity ( = 0.20, = 0.03, = 29). Despite 34% ( = 0.004) fewer LDs, the diameter of individual subsarcolemmal LDs was 20% ( = 0.0004) larger in type 2 fibers than in type 1 fibers. Furthermore, aerobic training decreased the size of subsarcolemmal LDs in the type 2 fibers, and ESA treatment lowered the number of both intermyofibrillar and subsarcolemmal LDs in the type 1 fibers. In conclusion, the size of individual subsarcolemmal LDs may be involved in the mechanism by which LDs are associated with insulin resistance in skeletal muscle.

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Morphometric documentation of abnormal intramyocellular fat storage and reduced glycogen in obese patients with Type II diabetes

Cited by 95 publications

References 33 publications

The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes

The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes

Metabolomics Approach for Analyzing the Effects of Exercise in Subjects with Type 1 Diabetes Mellitus

Lipid droplet size and location in human skeletal muscle fibers are associated with insulin sensitivity

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