Combining Various Methods to Assess Insulin Sensitivity in Nonobese Rat after Sleeve Gastrectomy

Abstract

Background Sleeve gastrectomy (SG) procedure has been proved to improve insulin sensitivity and sustain anti-diabetic effects. Our aim is to co-use several methods to measure insulin sensitivity and investigate the effect of SG on hepatic and peripheral insulin sensitivity at early and long-term stages of postoperation.

Methods Thirty 11-week-old male Goto-Kakizaki rats were divided into SG, sham-operated SG (SOSG), and control groups. They were observed before operation and for 36 weeks of postoperation. Insulin tolerance test (ITT) and homeostasis model of assessment for insulin resistance index(HOMA-IR)were used to measure insulin resistance before operations and at 2 and 36 weeks of postoperation; Pyruvate challenge test (PCT) was administrated to assess the gluconeogenesis capability in order to reflect hepatic insulin sensitivity before operation and at 2 and 36 weeks of postoperation; Hyperinsulinemic euglycemic clamps (HIEC) was conducted before operation and at 2 and 36 weeks of postoperation to calculate the endogenous hepatic glucose production (HGP) at the basal and steady-state for evaluation of hepatic insulin sensitivity, and calculate the exogenous glucose infusion rate (GIR) at the steady-state for evaluation of peripheral insulin sensitivity.

Results The data showed that compared with rats in the sham and control groups, rats in SG group had 1) significantly lower AUC_ITT, HOMA-IR and AUC _PCT values at 2 and 36 weeks of postoperation, 2) lower basal state HGP, but not steady-state GIR at 2 weeks of postoperation, and 3) significantly different basal and steady-state HGP and steady-state GIR at 36 weeks of postoperation. In addition, the basal and steady-state HGP and the steady-state GIR were significantly different between rats in SG group at 2 and 36 weeks of postoperation.

Conclusions This study explored insulin sensitivity of rats after SG by jointly using a variety of techniques. The results showed that SG time-dependently improved the hepatic and peripheral insulin sensitivity.

Key words

Sleeve gastrectomy - Insulin sensitivity - Goto-Kakizaki rats

• References

• 1 Sjöström L, Lindroos AK, Peltonen M. et al. Lifestyle, diabetes,and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351: 2683-2693
• 2 Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg 2013; 23: 427-436
• 3 Wu Q, Zhang X, Zhong M. et al. Effects of bariatric surgery on serum bile acid composition and conjugation in a diabetic rat model. Obes Surg 2016; 26: 2384-2392
• 4 Schauer PR, Kashyap SR, Wolski K. et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012; 366: 1567-1576
• 5 Yip S, Plank LD, Murphy R. Gastric bypass and sleeve gastrectomy for type 2 diabetes: A systematic review and meta-analysis of outcomes. Obes Surg 2013; 23: 1994-2003
• 6 Vidal J, Ibarzabal A, Romero F. et al. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects. Obes Surg 2008; 18: 1077-1082
• 7 Wilcox G. Insulin and insulin resistance. Clin Biochem Rev 2005; 26: 19-39
• 8 Sun D, Liu S, Zhang G. et al. Sub-sleeve gastrectomy achieves good diabetes control without weight loss in a non-obese diabetic rat model. Surg Endosc 2014; 28: 1010-1018
• 9 Sun D, Liu S, Zhang G. et al. Type 2 diabetes control in a nonobese rat model using sleeve gastrectomy with duodenal-jejunal bypass (SGDJB). Obes Surg 2012; 22: 1865-1873
• 10 Ayala JE, Bracy DP, Malabanan C et al. Hyperinsulinemic-euglycemic clamps in conscious, unrestrained mice. J Vis Exp 2011; 16: pii: 3188
• 11 de Bona Castelan J, Bettiol J, d'Acampora AJ. et al. Sleeve gastrectomy model in Wistar rats. Obes Surg 2007; 17: 957-961
• 12 Pereferrer FS, Gonzàlez MH, Rovira AF. et al. Influence of sleeve gastrectomy on several experimental models of obesity: Metabolic and hormonal implications. Obes Surg 2008; 18: 97-108
• 13 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
• 14 Rodgers JT, Puigserver P. Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc Natl Acad Sci USA 2007; 31104: 12861-12866
• 15 Abbatini F, Rizzello M, Casella G. et al. Long-term effects of laparoscopicsleeve gastrectomy, gastric bypass, and adjustable gastric banding on type 2 diabetes. Surg Endosc 2010; 24: 1005-1010
• 16 Karamanakos SN, Vagenas K, Kalfarentzos F. et al. Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Ann Surg 2008; 247: 401-407
• 17 Basso N, Capoccia D, Rizzello M. et al. First-phase insulin secretion,insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: The gastric hypothesis. Surg Endosc 2011; 25: 3540-3550
• 18 Tymitz K, Engel A, McDonough S. et al. Changes in ghrelin levels following bariatric surgery: Review of the literature. Obes Surg 2011; 21: 125-130
• 19 Dezaki K, Sone H, Yada T. Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis. Pharmacol Ther 2008; 118: 239-249
• 20 Monzillo LU, Hamdy O. Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev 2003; 61: 397-412
• 21 Gelding SV, Robinson S, Lowe S. et al. Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity. Clin Endocrinol (Oxf) 1994; 40: 611-615
• 22 Liu S, Zhang G, Wang L. et al. The entire small intestine mediates the changes in glucose homeostasis after intestinal surgery in Goto-Kakizaki rats. Ann Surg 2012; 256: 1049-1058
• 23 Yan Z, Chen W, Liu S. et al. Myocardial insulin signaling and glucose transport are up-regulated in Goto-Kakizaki type 2 diabetic rats after ileal transposition. Obes Surg 2012; 22: 493-501
• 24 Chen W, Yan Z, Liu S. et al. The changes of pro-opiomelanocortin neurons in type 2 diabetes mellitus rats after ileal transposition: the role of POMC neurons. J Gastrointest Surg 2011; 15: 1618-1624
• 25 Li F, Zhang G, Liang J. et al. Sleeve gastrectomy provides a better control of diabetes by decreasing ghrelin in the diabetic Goto-Kakizaki rats. J Gastrointest Surg 2009; 13: 2302-2308
• 26 Ballantyne GH, Wasielewski A, Saunders JK. The surgical treatment of type II diabetes mellitus: Changes in HOMA Insulin resistance in the first year following laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB). Obes Surg 2009; 19: 1297-1303
• 27 Troy S, Soty M, Ribeiro L. et al. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastriclap-band in mice. Cell Metab 2008; 8: 201-211
• 28 Yassin K, Huyen VT, Hoa KN. et al. Herbal extract of gynostemma pentaphyllum decreases hepatic glucose output in type 2 diabetic goto-kakizaki rats. Int J Biomed Sci 2011; 7: 131-136