Dynamics of Total Volume of Pancreatic α- and β -cells Under the Influence Sulfonylureas and Their Combination with Dipeptidyl Peptidase-4 Inhibitors

Overview

Journal Endocrinol Diabetes Metab

Specialty Endocrinology

Date 2021 Jul 19

PMID 34277963

Citations 1

Authors

Tuchina Taisiia Pavlovna

Skotnikova Kseniia Petrovna

Vtorushina Anna Anatolievna

Uskov Ivan Sergeyevich

Rogoza Olga Vladimirovna

Grozov Roman Viktorovich

Babenko Alina Yurievna

Galagudza Mikhail Mikhailovich

Affiliations

Soon will be listed here.

Abstract

Objective: Sulfonylureas and dipeptidyl peptidase-4 inhibitors have a multidirectional effect on pancreatic cells. We aimed to evaluate the effects of these drugs on β- and α-cells in rats aged 12 months with type 2 diabetes mellitus when administered in combination with various sulfonylureas.

Methods: Streptozotocin-nicotinamide induced type 2 diabetes mellitus was induced in rats aged 12 months. Animals received the sulfonylureas gliclazide or glibenclamide for 24 weeks alone or in combination with the dipeptidyl peptidase-4 inhibitor vildagliptin or vildagliptin monotherapy. Blood glucose and animal weights were measured before and during the experiment. The oral glucose tolerance test was conducted before therapy initiation. Immunohistochemical analyses were conducted after the end of the experiment using glucagon and insulin antibodies. The total volumes of α and β cells were estimated in relation to the volume of the pancreatic islets.

Results: The total volumes of β-cells did not differ between the sulfonylurea group and the untreated type 2 diabetes mellitus group. The addition of dipeptidyl peptidase-4 inhibitors to sulfonylureas normalized the total volumes of β cells. The total volumes of α-cells in the gliclazide group and combination of gliclazide with dipeptidyl peptidase-4 inhibitor was comparable to that in the control group of intact animals, in contrast with the glibenclamide group.

Conclusion: The combination of vildagliptin to both sulfonylureas contributed to the normalisation of β-cells number. Normalisation of the total volumes of α-cells was observed with gliclazide therapy and combination of gliclazide with dipeptidyl peptidase-4 inhibitor.

Citing Articles

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PMID: 38038863 DOI: 10.1007/s13577-023-01007-0.

References

Sawada F, Inoguchi T, Tsubouchi H, Sasaki S, Fujii M, Maeda Y . Differential effect of sulfonylureas on production of reactive oxygen species and apoptosis in cultured pancreatic beta-cell line, MIN6. Metabolism. 2008; 57(8):1038-45. DOI: 10.1016/j.metabol.2008.01.038. View

Bayrasheva V, Babenko A, Dobronravov V, Dmitriev Y, Chefu S, Pchelin I . Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes. J Diabetes Res. 2017; 2016:8317850. PMC: 5206480. DOI: 10.1155/2016/8317850. View

Remedi M, Nichols C . Chronic antidiabetic sulfonylureas in vivo: reversible effects on mouse pancreatic beta-cells. PLoS Med. 2008; 5(10):e206. PMC: 2573909. DOI: 10.1371/journal.pmed.0050206. View

Ellingsgaard H, Hauselmann I, Schuler B, Habib A, Baggio L, Meier D . Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011; 17(11):1481-9. PMC: 4286294. DOI: 10.1038/nm.2513. View

Gromada J, Franklin I, Wollheim C . Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev. 2007; 28(1):84-116. DOI: 10.1210/er.2006-0007. View

Rizzo M, Barbieri M, Marfella R, Paolisso G . Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012; 35(10):2076-82. PMC: 3447848. DOI: 10.2337/dc12-0199. View

Talchai C, Xuan S, Lin H, Sussel L, Accili D . Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell. 2012; 150(6):1223-34. PMC: 3445031. DOI: 10.1016/j.cell.2012.07.029. View

Kim J, Kang S, Seo B, Choi H, Choi H, Ku S . Anti-diabetic activity of SMK001, a poly herbal formula in streptozotocin induced diabetic rats: therapeutic study. Biol Pharm Bull. 2006; 29(3):477-82. DOI: 10.1248/bpb.29.477. View

Dachicourt N, Bailbe D, Gangnerau M, Serradas P, Ravel D, Portha B . Effect of gliclazide treatment on insulin secretion and beta-cell mass in non-insulin dependent diabetic Goto-Kakisaki rats. Eur J Pharmacol. 1998; 361(2-3):243-51. DOI: 10.1016/s0014-2999(98)00718-3. View

10.

Taylor B, Liu F, Sander M . Nkx6.1 is essential for maintaining the functional state of pancreatic beta cells. Cell Rep. 2013; 4(6):1262-75. PMC: 4058003. DOI: 10.1016/j.celrep.2013.08.010. View

11.

Islam M, Choi H . Nongenetic model of type 2 diabetes: a comparative study. Pharmacology. 2007; 79(4):243-9. DOI: 10.1159/000101989. View

12.

Zykov V, Tuchina T, Lebedev D, Krylova I, Babenko A, Kuleshova E . Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus. World J Diabetes. 2018; 9(9):149-156. PMC: 6153122. DOI: 10.4239/wjd.v9.i9.149. View

13.

Puri S, Akiyama H, Hebrok M . VHL-mediated disruption of Sox9 activity compromises β-cell identity and results in diabetes mellitus. Genes Dev. 2013; 27(23):2563-75. PMC: 3861670. DOI: 10.1101/gad.227785.113. View

14.

Butler A, Campbell-Thompson M, Gurlo T, Dawson D, Atkinson M, Butler P . Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013; 62(7):2595-604. PMC: 3712065. DOI: 10.2337/db12-1686. View

15.

Briant L, Reinbothe T, Spiliotis I, Miranda C, Rodriguez B, Rorsman P . δ-cells and β-cells are electrically coupled and regulate α-cell activity via somatostatin. J Physiol. 2017; 596(2):197-215. PMC: 5767697. DOI: 10.1113/JP274581. View

16.

Tsuchitani M, Sato J, Kokoshima H . A comparison of the anatomical structure of the pancreas in experimental animals. J Toxicol Pathol. 2016; 29(3):147-54. PMC: 4963614. DOI: 10.1293/tox.2016-0016. View

17.

Tesch G, Allen T . Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology (Carlton). 2007; 12(3):261-6. DOI: 10.1111/j.1440-1797.2007.00796.x. View

18.

Karimi S, Ai J, Khorsandi L, Bijan Nejad D, Saki G . Vildagliptin Enhances Differentiation of Insulin Producing Cells from Adipose-Derived Mesenchymal Stem Cells. Cell J. 2018; 20(4):477-482. PMC: 6099143. DOI: 10.22074/cellj.2019.5542. View

19.

Brereton M, Rohm M, Shimomura K, Holland C, Tornovsky-Babeay S, Dadon D . Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells. Nat Commun. 2016; 7:13496. PMC: 5123088. DOI: 10.1038/ncomms13496. View

20.

Cooperberg B, Cryer P . Beta-cell-mediated signaling predominates over direct alpha-cell signaling in the regulation of glucagon secretion in humans. Diabetes Care. 2009; 32(12):2275-80. PMC: 2782990. DOI: 10.2337/dc09-0798. View