Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity

ObjectiveBariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.DesignSubjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.ResultsWe observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.ConclusionAllogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.Trial registration numberNTR4327.

Download Full-text

Effect of needle biopsy from the vastus lateralis muscle on insulin-stimulated glucose metabolism in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.4.e544 ◽

1994 ◽

Vol 267 (4) ◽

pp. E544-E548 ◽

Cited By ~ 3

Author(s):

P. Holck ◽

N. Porksen ◽

M. F. Nielsen ◽

B. Nyholm ◽

J. F. Bak ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Metabolism ◽

Glucose Uptake ◽

Muscle Biopsy ◽

Needle Biopsy ◽

Vastus Lateralis ◽

Whole Body ◽

Vastus Lateralis Muscle ◽

Lateralis Muscle ◽

Glucose Output

To examine the cellular mechanisms behind conditions characterized by insulin resistance, the clamp technique is often combined with muscle biopsies. To test whether the trauma of a needle biopsy from the vastus lateralis muscle per se may influence insulin-stimulated glucose uptake, eight healthy subjects underwent two randomly sequenced hyperinsulinemic (insulin infusion rate: 0.6 mU.kg-1.min-1 for 150 min) euglycemic clamps with an interval of 4-6 wk. In one study (study B) a muscle biopsy (approximately 250 mg, i.e., larger than normal standard) was taken in the basal state just before the clamp procedure, whereas the other was a control study (study C). Insulin-stimulated glucose uptake was significantly reduced in study B (5.36 +/- 0.96 mg.kg-1.min-1) compared with study C (6.06 +/- 0.68 mg.kg-1.min-1; P < 0.05). Nonoxidative glucose disposal (indirect calorimetry) was decreased (2.81 +/- 1.08 vs. 3.64 +/- 1.34 mg.kg-1.min-1; P < 0.05), whereas glucose oxidation was unaltered. Likewise, endogenous glucose output ([3-3H]glucose) was identically suppressed during hyperinsulinemia. Circulating levels of epinephrine, glucagon, and growth hormone did not differ significantly in studies B and C. In contrast, plasma norepinephrine, serum cortisol, and free fatty acid rose after biopsy (P < 0.05). In conclusion, performance of a muscle biopsy may diminish insulin sensitivity by affecting nonoxidative glucose metabolism. This should be considered when assessing whole body insulin sensitivity after a percutaneous needle muscle biopsy.

Download Full-text

Glucose metabolism in epitrochlearis muscle of acutely exercised and trained rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.250.2.e137 ◽

1986 ◽

Vol 250 (2) ◽

pp. E137-E143 ◽

Cited By ~ 2

Author(s):

T. A. Davis ◽

S. Klahr ◽

E. D. Tegtmeyer ◽

D. F. Osborne ◽

T. L. Howard ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Metabolism ◽

Glucose Uptake ◽

Acute Exercise ◽

Glycogen Synthesis ◽

Prior Training ◽

Glycogen Stores

Effects of insulin on glycogen synthesis (GS), glycolytic utilization (GU), and glucose uptake (GT) were studied in isolated epitrochlearis muscles from exercise-trained or sedentary rats during recovery from acute exercise or at rest. During the 1st h after acute exercise, the enhanced basal and insulin-stimulated GT was directed mainly toward replenishment of glycogen but basal GU was also increased. During the second through third hours after exercise, basal GS decreased but remained greater than rest and basal GU and GT returned to normal. Insulin sensitivity of these parameters was enhanced. Training alone reduced basal GS but enhanced insulin sensitivity of GT and GU. Training reduced the acute exercise-stimulated increase in basal and insulin sensitivity of GS during recovery from acute exercise, probably due to elevated glycogen stores. Thus recovery from acute exercise or training, either alone or in combination, enhances insulin stimulated GT in muscle; however, the increased glucose is primarily channeled toward GS after acute exercise, which is reduced by prior training and is directed to GU in trained animals either at rest or after acute exercise.

Download Full-text

Habenula lesions improve glucose metabolism in rats with type 2 diabetes by increasing insulin sensitivity and inhibiting gluconeogenesis

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001250 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001250

Author(s):

Peng Qu ◽

Yachun Wang ◽

Lei Liu ◽

Mengmeng Qi ◽

Yimeng Sun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Nervous System ◽

Insulin Sensitivity ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Sham Group ◽

Adrenal Glands ◽

Tolerance Test ◽

Lesion Group

IntroductionThe habenular nucleus (Hb), a famous relay station in the midbrain, is vital for controlling many physiological functions of vertebrates. The role of Hb in the pathogenesis of depression has been thoroughly studied, but whether it functions in the pathogenesis of diabetes remains unknown. In this study, we found that Hb lesions could improve glucose metabolism in type 2 diabetes mellitus (T2DM) by inhibiting the peripheral sympathetic nervous system and hepatic glucose production.Research design and methodsT2DM rats were induced by a high-carbohydrate and fat diet combined with streptozotocin. Electrical lesion method was applied to suppress the function of Hb. Serum and tissue samples of rats in the control group, T2DM group, sham group, and Hb lesion group were detected by ELISA, western blotting, and biochemical methods.ResultsCompared with the sham group, the expression levels of AMPK phosphorylation and insulin receptor (IR) were significantly increased, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxylated kinase were reduced in the liver of the Hb lesion group. In the glucose tolerance test and pyruvate tolerance test, the lesion group showed stronger glucose tolerance and lower hepatic gluconeogenesis than the sham. These results suggest that Hb lesions not only effectively increase insulin sensitivity and improve insulin resistance but also inhibit gluconeogenesis in T2DM rats. Moreover, Hb lesions increase the expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, glucocorticoid receptor, and IR in the hippocampus. In this study, we also found that Hb lesions increase the content of acetylcholine in the adrenal glands and reduce the content of epinephrine in both the adrenal glands and the liver, which may be the main reason for the Hb lesions to regulate glucose metabolism in the liver.ConclusionHb is an important neuroanatomical target for the regulation of glucose metabolism in the central nervous system of diabetic rats.

Download Full-text

Does eating a reheated starchy carbohydrate meal improve postprandial glycaemia?

Proceedings of The Nutrition Society ◽

10.1017/s0029665120005807 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Tracey Robertson ◽

Jonathan Brown ◽

Barbara Fielding ◽

Nicola Jackson ◽

Roman Hovorka ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Metabolism ◽

Repeated Measures ◽

Postprandial Glucose ◽

Cooking Methods ◽

Postprandial Glycaemia ◽

Significant Difference ◽

Reheating Process ◽

Postprandial Insulin ◽

Carbohydrate Meal

AbstractIncreased postprandial glycaemia and reduced insulin sensitivity are associated with development of Type 2 Diabetes (T2D). Maintaining a normal glucose response is important both for healthy individuals, for disease prevention, and for those with T2D, to prevent development of diabetes-related complications. Chilling previously-cooked starchy carbohydrate (CHO) results in retrogradation of some of the starch to form resistant starch (RS). RS is not absorbed in the small intestine and consequently does not contribute to the postprandial glucose excursion. Reheating the CHO, however, reverses this process, reducing some of the RS content. RS type 5 is formed in the laboratory by heating starch with free fatty acids; there is limited evidence for its formation using domestic cooking methods and real foods. Furthermore it is unclear whether this would translate into a noticeable effect on postprandial glucose metabolism.In this randomised crossover study, 8 participants attended two study days; at one they consumed a freshly cooked mashed potato meal (203 g boiled potato, 25 g butter) at the other they consumed an identical meal which had been chilled for 66 h then microwave reheated. The potatoes were intrinsically labelled with [U-13C]starch, and participants received a variable [6,6-2H2]glucose infusion, allowing detailed glucose flux modelling. Venous blood samples were taken for 6 h postprandially.There was no significant effect on postprandial glucose, however repeated measures ANOVA on postprandial insulin time-point data found a significant difference between meals (p = 0.026), with a 24% reduction in incremental area under the curve (0–120 min) and 21% reduction in insulin peak between freshly cooked and reheated meals. There were no significant effects on rate of appearance of glucose into the plasma from the gut (Ra) or on endogenous (hepatic) glucose production (EGP), however there was a strong trend for a reduced rate of glucose disposal (uptake into tissues, Rd) following the reheated meal (p = 0.054).It is hypothesised that RS was formed in the reheated meal by the chilling and reheating process; this will be verified by in vitro work later in the project. The attenuation of the postprandial insulin response with no significant effect on EGP suggests enhanced hepatic insulin sensitivity following the reheated meal as a possible mechanism for the effects of RS on postprandial glycaemia. This study demonstrates that making simple changes to the way a starchy carbohydrate meal is prepared can have significant beneficial effects on postprandial glucose metabolism.

Download Full-text