Document Type : Original Article

Authors

1 Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming Yunnan, China

2 Medical School, Kunming Medical University, Kunming, Yunnan, China

3 Kunming Children’s Hospital, Kunming, Yunnan, China

4 HKU-Pasteur Research Pole, Hong Kong, China

5 Department of Physiology, School of Medicine, Tulane University, New Orleans, USA

6 Department of Pathology and Laboratory Medicine, Tulane University, New Orleans, USA

Abstract

Elevated blood glucose concentration due to food intake will trigger insulin secretion from the dorsal pancreas has been extensively studied. This increased intracellular insulin level can stimulate glucagon release from intra-islets. However, the interaction between glucagon and insulin under a fasting state is unknown. To explore the relationship, we partially removed the ventral and dorsal pancreas on wild-type adult rats. The glucose tolerance test was conducted to measure influence of the surgery on the integrity function of the pancreas. The fasting insulin/glucagon level before and after surgery were measured by the ELISA kit. The statistical analyses indicated that the ventral removal of the pancreas had higher fasting glucose than that of dorsal removal. And only the ventral removal group showed significantly increased basal insulin and basal glucagon levels. Our findings showed differential role of the ventral pancreas in response to a glucose-free stimulus and also provided the possible in vitro target for developing the anti-hyperglycemic drugs.

Keywords

  1. Curry DL, Bennett LL, Grodsky GM. Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology 1968; 83(83):572-584.
  2. Pipeleers DG. Heterogeneity in pancreatic beta-cell population. Diabetes 1992; 41(7):777-781.
  3. Trimble ER, Halban PA, Wollheim CB, et al. Functional differences between rat islets of ventral and dorsal pancreatic origin. J Clin Invest 1982; 69(2):405-413.
  4. Gerich JE. Is reduced first-phase insulin release the earliest detectable abnormality in individuals destined to develop type 2 diabetes? Diabetes 2002; 51 Suppl 1: S117-S121.
  5. Rubino F, Schauer PR, Kaplan LM, et al. Metabolic surgery to treat type 2 diabetes: clinical outcomes and mechanisms of action. Annu Rev Med 2010; 61: 393-411.
  6. Li M, Lu Y, Wang AR. View insulin resistance from an interaction between pancreatic islets and peripheral Clin Med Res 2018; 7(5): 124-130.
  7. Aberer F, Theiler-Schwetz V, Ziko H, et al. Accuracy and stability of an arterial sensor for glucose monitoring in a porcine model using glucose clamp technique. Sci Rep 2020; 10(1): 6604. doi: 10.1038/s41598-020-63659-4.
  8. Bergman RN, Prager R, Volund A, et al. Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. J Clin Invest 1987; 79(3): 790-800.
  9. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237(3): E214-E223.
  10. Hughey CC, Hittel DS, Johnsen VL, et al. Hyper-insulinemic-euglycemic clamp in the conscious rat. J Vis Exp 2011; (48): 2432. doi: 10.3791/2432.
  11. Yamamoto K, Takeda N, Yamatodani A. Establishment of an animal model for radiation-induced vomiting in rats using pica. J Radiat Res 2002; 43(2): 135-141.
  12. Bowe JE, Franklin ZJ, Hauge-Evans AC, et al. Metabolic phenotyping guidelines: assessing glucose homeostasis in rodent models. J Endocrinol 2014; 222(3): G13-G25.
  13. Machholz E, Mulder G, Ruiz C, et al. Manual restraint and common compound administration routes in mice and rats.J Vis Exp 2012; (67): 2771. doi: 10.3791/2771.
  14. Carter JD, Dula SB, Corbin KL, et al. A practical guide to rodent islet isolation and assessment. Biol Proced Online 2009; 11: 3-31.
  15. Struck MB, Andrutis KA, Ramirez HE, et al. Effect of a short-term fast on ketamine-xylazine anesthesia in rats. J Am Assoc Lab Anim Sci 2011; 50(3): 344-348.
  16. Morris TH. Antibiotic therapeutics in laboratory-animals. Lab Anim 1995; 29(1): 16-36.
  17. Tsai PP, Schlichtig A, Ziegler E, et al. Effects of different blood collection methods on indicators of welfare in mice. Lab Anim 2015; 44: 301-310.
  18. Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother 2010; 1(2): 87-93.
  19. Kanat M, Norton L, Winnier D, et al. Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose. Acta Diabetol 2011; 48(3): 209-217.
  20. Olefsky JM. Lilly lecture 1980. Insulin resistance and insulin action. An in vitro and in vivo perspective. Diabetes 1981; 30(2):148-162.
  21. Kara ME. The anatomical study on the rat pancreas and its ducts with emphasis on the surgical approach. Ann Anat 2005; 187(2): 105-112.
  22. Hutchison AT, Regmi P, Manoogian ENC, et al. Time‐restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial. Obesity (Silver Spring) 2019; 27(5): 724-732.
  23. Jensen TL, Kiersgaard MK, Sørensen DB, et al. Fasting of mice: a review. Lab Anim 2013; 47(4): 225-240.
  24. Ruiter M, La Fleur SE, van Heijningen C, et al. The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior. Diabetes 2003; 52(7): 1709-1715.