Effects of Rat C-peptide-II on Lipolysis and Glucose Consumption in Cultured Rat Adipose Tissue

 

 Buy Article Permissions and Reprints

Abstract

Existing data show that C-peptide (CP) prevents or ameliorates diabetes-related complications mainly by improving microcirculation and perhaps metabolism. Although effects of CP on muscle glucose consumption are relatively well studied, its effects on adipose tissue, a key organ involved in metabolism, are not well known. Therefore, the aim of this study was to examine the effects of CP on basal and stimulated lipolysis and glucose consumption in rat retroperitoneal (RP) adipose tissue, using an ex-vivo organ culture setting. The RP adipose tissue was excised from adult male rats, minced and subjected to ex-vivo culture for 24 h. The tissue fragments were then weighted and distributed into a 24-well culture plate. The wells were left untreated (basal) or treated with insulin or isoproternol (ISO, stimulated) and incubated in the absence or presence of CP, insulin or a combination of the both peptides. Levels of lipolysis and tissue glucose consumption were determined by glycerol and glucose concentrations measurement in the infranatant conditioned media collected from each well. The CP, like insulin, induced an insignificant reduction in basal lipolysis. While insulin significantly reduced the ISO-stimulated lipolysis, CP was ineffective. Tissue glucose consumption was significantly stimulated by insulin, but was not affected by CP. However, in the presence of CP, inhibitory effect on ISO-stimulated lipolysis and stimulatory effect on glucose consumption of insulin were significantly diminished. Our data suggest that CP may conditionally modulate certain metabolic actions of insulin in RP adipose tissue. These modulations may contribute to fine-tuning of body metabolism under physiologic or pathologic conditions.

References

• 1 Wahren J, Ekberg K, Jornvall H. C-peptide is a bioactive peptide.  Diabetologia. 2007;  50 503-509
  Google Scholar
• 2 Wahren J. C-peptide: new findings and therapeutic implications in diabetes.  Clin Physiol Funct Imaging. 2004;  24 180-189
  Google Scholar
• 3 Tsimaratos M, Roger F, Chabardes D. et al . C-Peptide stimulates Na⁺, K⁺-ATPase activity via PKC alpha in rat medullary thick ascending limb.  Diabetologia. 2003;  46 124-131
  Google Scholar
• 4 Wallerath T, Kunt T, Forst T. et al . Stimulation of endothelial nitric oxide synthase by proinsulin C-peptide.  Nitric oxide. 2003;  9 95-102
  Google Scholar
• 5 Shafqat J, Juntti-Berggren L, Zhong Z. et al . Proinsulin C-peptide and its analogues induce intracellular Ca⁺⁺ increases in human renal tubular cells.  Cell Mol Life Sci. 2002;  59 1185-1189
  Google Scholar
• 6 Nordquist L, Palm F, Andresen TB. Renal and vascular benefits of C-peptide: Molecular mechanisms of C-peptide action.  Biologics. 2008;  2 441-452
  Google Scholar
• 7 Uruska A, Araszkiewicz A, Zozulinska-Ziolkiewicz D. et al . Insulin resistance is associated with microangiopathy in type 1 diabetic patients treated with intensive insulin therapy from the onset of disease.  Exp Clin Endocrinol Diabetes. 2010;  118 478-484
  Google Scholar
• 8 Wu W, Oshida Y, Yang WP. et al . Effect of C-peptide administration on whole body glucose utilization in STZ-induced diabetic rats.  Acta Physiol Scand. 1996;  157 253-258
  Google Scholar
• 9 Zierath JR, Handberg A, Tally M. et al . C-peptide stimulates glucose transport in isolated human skeletal muscle independent of insulin receptor and tyrosine kinase activation.  Diabetologia. 1996;  39 306-313
  Google Scholar
• 10 Zierath JR, Galuska D, Johansson BL. et al . Effect of human C-peptide on glucose transport in in vitro incubated human skeletal muscle.  Diabetologia. 1991;  34 899-901
  Google Scholar
• 11 Johansson BL, Sjoberg S, Wahren J. The influence of human C-peptide on renal function and glucose utilization in type 1 (insulin-dependent) diabetic patients.  Diabetologia. 1992;  35 121-128
  Google Scholar
• 12 Grunberger G, Qiang X, Li Z. et al . Molecular basis for the insulinomimetic effects of C-peptide.  Diabetologia. 2001;  44 1247-1257
  Google Scholar
• 13 Rigler R, Pramanik A, Jonasson P. et al . Specific binding of proinsulin C-peptide to human cell membranes.  PNAS. 1999;  96 13318-13323
  Google Scholar
• 14 Ido Y, Vindigni A, Chang K. et al . Prevension of vascular and nural dysfunction in diabetic rats by C-peptide.  Sience. 1997;  277 563-566
  Google Scholar
• 15 Arner P. Human fat cell lipolysis: Biochemistry, regulation and clinical role.  Best Pract Res Clin Endocrinol Metab. 2005;  19 471-482
  Google Scholar
• 16 Adachi Y, Sakurai H. Insulin-mimetic vanadyl(IV) complexes as evaluated by both glucose-uptake and inhibition of free fatty acids (FFA) – release in isolated rat adipocytes.  Chem Pharm Bull. 2004;  52 428-433
  Google Scholar
• 17 Accorsi PA, Gamberoni M, Isani G. et al . Leptin does not seem to influence glucose uptake by bovine mammary explants.  J Physiol Pharmacol. 2005;  56 689-698
  Google Scholar
• 18 Moustaid N, Jones BH, Taylor JW. Insulin increase lipogenic enzyme activity in human adipocytes in primary culture.  J Nutr. 1996;  126 865-870
  Google Scholar
• 19 Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis.  J Biol Chem. 1964;  239 375-380
  Google Scholar
• 20 Nakano T, Scott PG. Purification and characterization of gelatinase produced by fibroblasts from human gingival.  Biochem Cell Biol. 1986;  64 387-393
  Google Scholar
• 21 Kitabchi AE. The biological and immunological properties of pork and beef insulin, proinsulin, and connecting peptides.  J Clin Inves. 1970;  49 979-987
  Google Scholar
• 22 Solomon SS, Brush JS, Kitabchi AE. Antilipolytic activity of insulin and proinsulin on ACTH and cyclic nucleotide-induced lipolysis in the isolated adipose cell of rat.  Biochem Biophys Acta. 1970;  218 167-169
  Google Scholar
• 23 Yu SS, Kitabchi AE. Biological activity of proinsulin and related polypeptides in the fat tissue.  J Biol Chem. 1973;  248 3753-3761
  Google Scholar
• 24 Steiner DF, Bell GI, Rubenstein AH. et al .Chemistry and biosynthesis of the islet hormones.. In: DeGroot L, Jameson JL Endocrinology 5th ed. Philadelphia: Elsevier; 2006: 925-960
  Google Scholar
• 25 Grunberger G, Sima AAF. The C-peptide signaling.  Exp Diab Res. 2004;  5 25-36
  Google Scholar
• 26 Horwitz DL, Starr JI, Mako ME. et al . Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood.  J Clin Invest. 1975;  55 1278-1283
  Google Scholar
• 27 Wahren J, Ekberg K, Johansson J. et al . Role of C-peptide in human physiology.  Am J Physiol Endocrinol Metab. 2000;  278 759-768
  Google Scholar
• 28 Ghorbani A, Varedi M, Hadjzadeh MA. et al . Type-1 diabetes induces depot-specific alterations in adipocyte diameter and mass of adipose tissues in the rat.  Exp Clin Endocrinol Diabetes. 2010;  118 442-448
  Google Scholar
• 29 Varedi M, Tredget EE, Ghahary A. et al . Stress-relaxation and contraction of a collagen matrix induces expression of TGF-β and triggers apoptosis in dermal fibroblasts.  Biochem Cell Biol. 2000;  78 427-436
  Google Scholar
• 30 Foster DW, Esser V. Ketoacidosis and hyperosmolar coma.. In: DeGroot L, Jameson JL, editors. Endocrinology 5 th ed. Philadelphia: Elsevier; 2006: 1185-1195
  Google Scholar
• 31 Kunt T, Schneider S, Pfutzner A. et al . The effect of human proinsulin C-peptide on erythrocyte deformability in patients with Type I diabetes mellitus.  Diabetologia. 1999;  42 465-471
  Google Scholar
• 32 Nordquist L, Moe E, Sjoquist M. The C-peptide fragment EVARQ reduces glomerular hyperfiltration in streptozotocin – induced diabetic rats.  Diabetes Metab Res Rev. 2007;  23 400-405
  Google Scholar

Correspondence

M. VarediPhD, Associate Professor 

Department of Physiology

Medical School

Shiraz University of Medical

Sciences

Shiraz, IRAN

Phone: +98/0711/230 2026

Fax: +98/0711/230 2026

Email: ghorbani_ahmad@yahoo.com