The effect of insulin on human small intestinal mucosal protein synthesis

Charlton, Michael; Ahlman, B.; Nair, K. Sreekumaran

doi:10.1016/s0016-5085(00)70212-5

Cited by 46 publications

(25 citation statements)

References 32 publications

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“…These results are consistent with the previous interorgan studies demonstrating insulin's inhibitory effect on splanchnic protein synthesis (8,9). Studies performed in patients with diabetes suggest that these changes in protein synthesis do not occur in the gut (45) and thus occur in the liver. Studies in rodents also suggest that insulin deprivation or insulin administration has no effect on liver protein synthesis (3,46,47).…”

Section: Discussionsupporting

confidence: 92%

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

et al. 2001

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In vivo studies have reported conflicting effects of insulin on mixed tissue protein synthesis rates. To test the hypothesis that insulin has differential effects on synthesis rates of various protein fractions in different organs, we infused miniature swine (n ‫؍‬ 8 per group) with saline, insulin alone (at 0.7 mU/kg ؊1 ⅐ min ؊1 ), or insulin plus an amino acid mixture for 8 h. Fractional synthesis rate (FSR) of mitochondrial and cytoplasmic proteins in liver, heart, and skeletal muscle, as well as myosin heavy chain (MHC) in muscle, were measured using L-[1-13 C]leucine as a tracer. The FSR of mitochondrial and cytoplasmic proteins were highest in liver, followed by heart and then muscle. Mitochondrial FSR in muscle was higher during insulin and insulin plus amino acid infusions than during saline. Insulin had no significant effect on FSR of MHC in muscle. In contrast, FSR of both mitochondrial and cytoplasmic proteins were not stimulated by insulin in liver. Insulin also did not increase FSR of mitochondrial in heart, whereas insulin and amino acid stimulated FSR of cytoplasmic protein. In conclusion, insulin stimulates the synthesis of muscle mitochondrial proteins, with no significant stimulatory effect on synthesis of sarcoplasmic and MHC. These results demonstrate that insulin has different effects on synthesis rates of specific protein fractions in the liver, heart, and skeletal muscle. Diabetes

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Section: Discussionsupporting

confidence: 92%

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

et al. 2001

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“…In this study, the blood glucose concentration was four to five times higher in diabetic rats than in non-diabetic rats. Many studies have shown that experimental Type 1 diabetes causes morphological, functional, and metabolic alterations in the small intestine [2,3,5,6,7,8,9,10,23]. The major findings in this study were that the opening angle and residual strain were lower in the duodenum and larger in the jejunum and ileum in diabetic rats compared to normal rats.…”

Section: Resultssupporting

confidence: 46%

“…The main metabolic complications of diabetes are retinopathy, nephropathy and peripheral vasculopathy. Gastrointestinal (GI) by STZ is characterised by morphological GI remodelling such as proliferation of different layers, especially of the mucosa in the small intestine [5,6,7,8,9,10]. Because morphological remodelling of the small intestine occurs in diabetes, the biomechanical properties are also likely to change.…”

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confidence: 99%

Biomechanical and morphometric intestinal remodelling during experimental diabetes in rats

2003

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Aims/hypothesis. Morphometric and passive biomechanical properties were studied in the duodenum, jejunum and ileum in 10 non-diabetic and 40 streptozotocin-induced diabetic rats. Methods. The diabetic rats were divided into groups living 4 days, 1, 2, and 4 weeks after diabetes was induced (n=10 for each groups). The mechanical test was done as a ramp distension experiment. The intestinal diameter and length were obtained from digitised images of the intestinal segments at pre-selected pressures and at no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state geometry. Results. The blood glucose concentration increased four-to fivefold in the diabetic rats. Streptozotocin-induced diabetes generated pronounced increase in the weight per centimetre length, wall thickness and wall cross-sectional area in all intestinal segments during diabetes (p<0.05). Histological analysis showed that the thickness of the intestinal layers was increased in all segments during diabetes (p<0.05). In the duodenum the opening angle did not change in the first 2 weeks and decreased after 4 weeks (p<0.05). In the jejunum and ileum the opening angle increased after 1 week in the diabetic group. The residual strain showed the same pattern as the opening angle. Furthermore, it was found that the circumferential and longitudinal stiffness of the intestinal wall increased with the duration of diabetes (p<0.05 and p<0.01). Conclusion/interpretation. Morphological and biomechanical remodelling of the small intestine occurred during the development of diabetes. [Diabetologia (2003[Diabetologia ( ) 46:1688[Diabetologia ( -1697

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“…Insulin may contribute, in part, to glutamine and amino acid effects on FSR, because a moderate increase of plasma insulin concentration was observed after both glutamine and amino acid infusion. Indeed, recent data indicate that insulin can support intestinal protein synthesis (6). On the other hand, insulin reduces muscular ATP-ubiquitin-dependent proteolytic pathway activity (10); however, in the present study, the inhibiting effect of glutamine on intestinal ubiquitin mRNA is unlikely mediated by insulin, because insulin was not differentially affected by glutamine compared with amino acid mixture infusion.…”

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confidence: 67%

Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa

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Claeyssens

Hecketsweiler

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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chelotte. Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa. Am J Physiol Gastrointest Liver Physiol 285: 266-G273, 2003. First published April 17, 2003 10.1152/ ajpgi.00385.2002.-Effects of glutamine on whole body and intestinal protein synthesis and on intestinal proteolysis were assessed in humans. Two groups of healthy volunteers received in a random order enteral glutamine (0.8 mmol ⅐ kg body wt Ϫ1 ⅐ h Ϫ1 ) compared either to saline or isonitrogenous amino acids. Intravenous [ 2 H5]phenylalanine and [ 13 C]leucine were simultaneously infused. After gas chromatography-mass spectrometry analysis, whole body protein turnover was estimated from traced plasma amino acid fluxes and the fractional synthesis rate (FSR) of gut mucosal protein was calculated from protein and intracellular phenylalanine and leucine enrichments in duodenal biopsies. mRNA levels for ubiquitin, cathepsin D, and m-calpain were analyzed in biopsies by RT-PCR. Glutamine significantly increased mucosal protein FSR compared with saline. Glutamine and amino acids had similar effects on FSR. The mRNA level for ubiquitin was significantly decreased after glutamine infusion compared with saline and amino acids, whereas cathepsin D and m-calpain mRNA levels were not affected. Enteral glutamine stimulates mucosal protein synthesis and may attenuate ubiquitin-dependent proteolysis and thus improve protein balance in human gut. intestine; protein metabolism; nutrients GLUTAMINE IS THE MAJOR FUEL for enterocytes, and it promotes intestinal growth and metabolism and maintains the structure and function of intestinal mucosa, especially in situations of gut injury (38) or after gut resection in animals (37). In vitro, glutamine stimulated intestinal cell proliferation (33). Numerous studies have reported the benefits of a glutamine enteral or parenteral nutritional supplementation on gut barrier (20,42). In animal studies, glutamine supply decreased the alterations of gut mucosa induced by prolonged starvation (20) or an experimental enterocolitis (2) by increasing the weight of the mucosa, the height of villi, and DNA and protein content. In humans, glutamineenriched parenteral nutrition maintained villus height and limited the increase of gut permeability (42). Treatment of patients with glutamine, growth hormone, and diet modifications after gut resection was reported to be beneficial on water and electrolyte absorption in an early uncontrolled study (5), but this has not been confirmed by more recent controlled studies (36).Additionally, enteral infusion of a high glutamine load in volunteers altered whole body leucine fluxes in a manner indicating a reduced protein oxidation and an increased protein synthesis (16). The beneficial effects of glutamine on gut mucosa could be partly due to a stimulation of protein synthesis as shown in animal studies, in vitro (17) and in vivo (41). In previous studies, we have shown that glutamine was well absorbed in human intestine (13) and stimulated ϳ40% duoden...

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The effect of insulin on human small intestinal mucosal protein synthesis

Cited by 46 publications

References 32 publications

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

Biomechanical and morphometric intestinal remodelling during experimental diabetes in rats

Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa

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