Skip to main content
SpringerLink
Log in

The effect of prolonged hyperglycemia on metabolic alterations in the subtotally pancreatectomized rat

  • Original Articles
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

A delayed onset of diabetes is characteristic of subtotally pancreatectomized patients in whom persistent hyperglycemia per se is documented to lead to the development of insulin resistance. This study was conducted to elucidate the metabolic alterations seen during transition of the acute to chronic phase after subtotal pancreatectomy (SP). Eight male Sprague-Dawley rats were studied 2 weeks after surgery in the acute phase, and the other eight at 4 weeks in the chronic phase. Phosphoenolpyruvate carboxykinase (PEPck) for gluconeogenesis and the malic enzyme for de novo fatty acid synthesis in the liver showed a reciprocal change, the former activity being increased, while the latter was suppressed. Both alterations were more pronounced in the chronic phase. In the acute phase, lipoprotein lipase (LPL) for triglyceride clearance decreased in the adipose tissue, while that in the cardiac and skeletal muscle became significantly elevated. The latter elevations were decreased in the chronic phase. Sustained hyperglycemia in the SP rats not only increased the changes in PEPck and malic enzyme activities but reversed the tissue-specific muscle LPL elevations. These changes might help to explain the wasting condition seen in surgically induced diabetic patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Appleby LH (1953) The celiac axis in the expansion of the operation for gastric cancer. Cancer 6:704–727

    PubMed  Google Scholar 

  2. Sandmeyer W (1893) Über die Folgen der Pankreasextirpation beim Hund. Ztsch F Biol 11:86–114

    Google Scholar 

  3. Reaven GM, Sageman WS, Swenson RS (1977) Development of insulin resistance in normal dogs following alloxan-induced insulin deficiency. Diabetologia 13:459–462

    Article  PubMed  Google Scholar 

  4. Pupo AA, Ursich MJM, Iamaguchi, Vasconcellos FG (1976) Acute and late phase insulin secretion and glucose tolerance in mild alloxan diabetes dog. Diabetes 25:161–166

    PubMed  Google Scholar 

  5. Beviloqua SD, Barrett EJ, Smith D, Simpson DC, BratuschMarrain D, Ferrannini E, DeFronzo RA (1985) Hepatic and peripheral insulin resistance following streptozotocin-induced insulin deficiency in the dog. Metab Clin Exp 34:817–825

    PubMed  Google Scholar 

  6. Lery J. Gavin III Jr, Fausto A, Gingerich RL, Avioli LV (1984) Impaired insulin action in rats with non-insulin dependent diabetes. Diabetes 33:901–906

    PubMed  Google Scholar 

  7. Dall'Aglio E, Chang H, Hollenbeck CB, Mondon CE, Sims C, Reaven GM (1985) In vivo and in vitro resistance to maximal insulin stimulated glucose disposal in insulin deficiency. Am J Physiol 249:E312-E316

    PubMed  Google Scholar 

  8. Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA (1987) Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 79:1510–1515

    PubMed  Google Scholar 

  9. Foglia VG (1944) Ca de la diabetes en la rata. Rev Soc Angent Biol 20:21–37

    Google Scholar 

  10. Benner-Wein S, Trent DF, Weir GC (1983) Partial pancreatectomy in the rats and subsequent defect in glucose induced insulin release. J Clin Invest 71:1544–1553

    PubMed  Google Scholar 

  11. Bucolo G, David H (1973) Quantitative determination of serumtriglycerides by the use of enzymes. Clin Chem 19:476–482

    PubMed  Google Scholar 

  12. Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein. utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    PubMed  Google Scholar 

  13. Albano LDM, Ekins RP, Maritz G, Turner RC (1972) A sensitive, precise radioimmunoassay or serum insulin relying on charcoal separation of bound and free moieties. Acta Endocr 70:487–509

    PubMed  Google Scholar 

  14. Chang HC, Lane MD (1966) The enzymatic carboxylating phosphoenolpyruvate 11. Purification and properties of liver mitochondria) phosphoenolpyruvate carboxykinase. J Biol Chem 241:2431–2440

    PubMed  Google Scholar 

  15. Hsu RY, Lardy HA (1969) Malic enzyme. Methods Enzymol 13:230–235

    Google Scholar 

  16. Nilsson-Ehle P, Schotz MC (1976) A stable radioactive substrate emulsion for assay of lipoprotein lipase. J Lipid Res 17:536–541

    PubMed  Google Scholar 

  17. Yonemura Y, Miyazaki I, Miwa K, Matsuki N, Takashima S (1981) The endocrine function of the pancreas after partial pancreatectomy. Nippon Geka Gakkai Zasshi (J Jpn Surg Soc) 82:671–680

    Google Scholar 

  18. Imamura T, Koffler M, Heldelman JH, Prince D, Thirbly R, Inman L, Unger RH (1988) Severe diabetes induced in subtotally depancreatized dogs by sustained hyperglycemia. Diabetes 37:600–609

    PubMed  Google Scholar 

  19. Lorenzi M, Montisano DF, Toledo S, Barrieux A (1986) High glucose-induced DNA damage in cultured human endothelial cells. J Clin Invest 77:322–325

    PubMed  Google Scholar 

  20. Bucola R, Model P, Russel M, Cerami A (1985) Modification of DNA by glucose-6-phosphate induces DNA rearrangements in an EScherichia coli plasmid. Proc Natl Acad Sci USA 82:8439–8442

    PubMed  Google Scholar 

  21. Nelson K, Cimbala MA, Hanson RW (1981) Regulation of the turnover of the mRNA for hepatic phosphoenolpyruvate carboxykinase (GTP). In: Venezialo CM (ed) The regulation of carbohydrate formation and utilization in mammals. University Park Press, Baltimore, pp 349–392

    Google Scholar 

  22. Wynshaw BA, Short JM, Loose DS, Hanson RW (1986) Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. I. Multiple hormone regulatory elements and the effects of enhancers. J Biol Chem 261:9714–9720

    PubMed  Google Scholar 

  23. Back DW, Wilson SB, Morris SM Jr, Goodridge AG (1986) Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. J Biol Chem 261:12555–12561

    PubMed  Google Scholar 

  24. Chu DT, Davis CM, Chraptiewicz NB, Granner DK (1988) Reciprocal regulation of gene transcription by insulin inhibition of the phosphoenolpyruvate carboxykinase gene and stimulator of gene 33 in a single cell type. J Biol Chem 263:13007–13001

    PubMed  Google Scholar 

  25. O'Looney P, Maten MV, Vahouny GV (1983) Insulin-mediated modification of myocardial lipoprotein lipase and lipoprotein metabolism. J Biol Chem 258:12994–13001

    PubMed  Google Scholar 

  26. Aktin E, Meng HC (1972) Release of clearing factor lipase (lipoprotein lipase) in vivo and from isolated perfusion hearts of alloxan diabetic rats. Diabetes 21:149–156

    PubMed  Google Scholar 

  27. Stam H, Schoonderwoerd K, Breeman W, Hulsmann WC (1984) Effects of hormones, fasting and diabetes on triglyceride lipase activities in rat heart and liver. Horm Metab Res 16:293–297

    PubMed  Google Scholar 

  28. Exton JH, Robinson GA, Sutherland EW, Park CR (1971) Studies on the role of adenosine 3',5'-monophosphate in the hepatic action of glucagon and catecholamines. J Biol Chem 246:6166–6177

    PubMed  Google Scholar 

  29. Mirouze J, Selam JL, Pham TC, Mendoza E, Orsetti A (1978) Sustained insulin-induced remissions of juvenile diabetes by means of an external artificial pancreas. Diabetologia 14:223–227

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Surgery, Yokohama City University School of Medicine, 3-9 Fukuura, 236, Kanazawa-ku, Yokohama, Japan

    Yoshikazu Noguchi & Akihiko Matsumoto

  2. Surgical Metabolism Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021, New York, NY, USA

    Yoshikazu Noguchi, Riad N. Younes, Kevin C. Conlon, Nadarajen A. Vydelingum & Murray F. Brennan

Authors
  1. Yoshikazu Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Riad N. Younes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kevin C. Conlon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nadarajen A. Vydelingum
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akihiko Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Murray F. Brennan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Noguchi, Y., Younes, R.N., Conlon, K.C. et al. The effect of prolonged hyperglycemia on metabolic alterations in the subtotally pancreatectomized rat. Surg Today 24, 987–993 (1994). https://doi.org/10.1007/BF02215812

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02215812

Key Words

Search

Navigation