Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1984 Apr 1;219(1):189–196. doi: 10.1042/bj2190189

Regulation of insulin secretion by energy metabolism in pancreatic B-cell mitochondria. Studies with a non-metabolizable leucine analogue.

U Panten, S Zielmann, J Langer, B J Zünkler, S Lenzen
PMCID: PMC1153464  PMID: 6372787

Abstract

In mouse pancreatic islets the kinetics of insulin secretion and O2 uptake in response to the non-metabolizable leucine analogue (+/-)-BCH (2-endo- aminonorbornane -2-carboxylic acid) were compared. In addition, the fuel-mobilizing effect of (+/-)-BCH was studied with a mitochondrial fraction from islets. (1) Within 2 min 20 mM-(+/-)-BCH markedly enhanced insulin release or O2 consumption by islets respiring in the absence of exogenous fuels. During prolonged exposure to 20 mM-(+/-)-BCH secretion declined more rapidly than O2 uptake. (2) L-Glutamine (10 mM) prevented the decrease of both insulin release and O2 uptake of islets exposed to 20mM-(+/-)-BCH. During the second phase of insulin release in response to 20 mM-(+/-)-BCH + 10 mM-L-glutamine, kinetics of secretion and respiration correlated closely. (3) Initial peaks were consistently seen in the (+/-)-BCH-induced secretory profiles, but never in the respiratory profiles. (4) In contrast with L-glycerol 3-phosphate, L-malate or pyruvate, L-glutamine or L-glutamate maintained low rates of oxidative phosphorylation in B-cell mitochondria. The effects of L-glutamine or L-glutamate were potentiated severalfold by (+/-)-BCH. (5) The effects of other branched-chain amino acids on oxidative phosphorylation resembled their effects on insulin release, redox state of nicotinamide nucleotides and glutamate dehydrogenase activity. (6) The results support the view that (+/-)-BCH stimulates insulin secretion via a primary enhancement of hydrogen supply to the respiratory chain of B-cell mitochondria.

Full text

PDF
189

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashcroft S. J., Weerasinghe L. C., Randle P. J. Interrelationship of islet metabolism, adenosine triphosphate content and insulin release. Biochem J. 1973 Feb;132(2):223–231. doi: 10.1042/bj1320223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernardi P., Azzone G. F. Regulation of Ca2+ efflux in rat liver mitochondria. Role of membrane potential. Eur J Biochem. 1983 Aug 1;134(2):377–383. doi: 10.1111/j.1432-1033.1983.tb07578.x. [DOI] [PubMed] [Google Scholar]
  3. Chay T. R., Keizer J. Minimal model for membrane oscillations in the pancreatic beta-cell. Biophys J. 1983 May;42(2):181–190. doi: 10.1016/S0006-3495(83)84384-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Christensen H. N., Hellman B., Lernmark A., Sehlin J., Tager H. S., Täljedal I. B. In vitro stimulation of insulin release by non-metabolizable, transport-specific amino acids. Biochim Biophys Acta. 1971 Aug 13;241(2):341–348. doi: 10.1016/0005-2736(71)90034-4. [DOI] [PubMed] [Google Scholar]
  5. Coore H. G., Randle P. J. Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochem J. 1964 Oct;93(1):66–78. doi: 10.1042/bj0930066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dean P. M. Ultrastructural morphometry of the pancreatic -cell. Diabetologia. 1973 Apr;9(2):115–119. doi: 10.1007/BF01230690. [DOI] [PubMed] [Google Scholar]
  7. GEPTS W., CHRISTOPHE J., MAYER J. Pancreatic islets in mice with the obese-hyperglycemic syndrome: lack of effect of carbutamide. Diabetes. 1960 Jan-Feb;9:63–69. doi: 10.2337/diab.9.1.63. [DOI] [PubMed] [Google Scholar]
  8. GRODSKY G. M., BATTS A. A., BENNETT L. L., VCELLA C., MCWILLIAMS N. B., SMITH D. F. EFFECTS OF CARBOHYDRATES ON SECRETION OF INSULIN FROM ISOLATED RAT PANCREAS. Am J Physiol. 1963 Oct;205:638–644. doi: 10.1152/ajplegacy.1963.205.4.638. [DOI] [PubMed] [Google Scholar]
  9. Gylfe E. Comparison of the effects of leucines, non-metabolizable leucine analogues and other insulin secretagogues on the activity of glutamate dehydrogenase. Acta Diabetol Lat. 1976 Jan-Apr;13(1-2):20–24. doi: 10.1007/BF02591577. [DOI] [PubMed] [Google Scholar]
  10. Holze S., Panten U. Studies on the role of beta-cell metabolism in the insulinotropic effect of alpha-ketoisocaproic acid. Biochim Biophys Acta. 1979 Dec 3;588(2):211–218. doi: 10.1016/0304-4165(79)90204-6. [DOI] [PubMed] [Google Scholar]
  11. Hutton J. C., Sener A., Malaisse W. J. The stimulus--secretion coupling 4-methyl-2-oxopentanoate-induced insulin release. Biochem J. 1979 Nov 15;184(2):303–311. doi: 10.1042/bj1840303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Idahl L. A., Hellman B. Regulation of pancreatic beta-cell glycogen through cyclic-3,5-AMP. Diabetologia. 1971 Jun;7(3):139–142. doi: 10.1007/BF01212544. [DOI] [PubMed] [Google Scholar]
  13. Joost H. G. Effects of possible beta-cell membrane label, metahexamide-isothiocyanate, on insulin release. Horm Metab Res. 1979 Feb;11(2):104–106. doi: 10.1055/s-0028-1092689. [DOI] [PubMed] [Google Scholar]
  14. KISSANE J. M., ROBINS E. The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem. 1958 Jul;233(1):184–188. [PubMed] [Google Scholar]
  15. Lenzen S., Formanek H., Panten U. Signal function of metabolism of neutral amino acids and 2-keto acids for initiation of insulin secretion. J Biol Chem. 1982 Jun 25;257(12):6631–6633. [PubMed] [Google Scholar]
  16. Lenzen S., Panten U. A versatile microfiltration device. Anal Biochem. 1983 Oct 1;134(1):56–59. doi: 10.1016/0003-2697(83)90263-4. [DOI] [PubMed] [Google Scholar]
  17. Lernmark A. The preparation of, and studies on, free cell suspensions from mouse pancreatic islets. Diabetologia. 1974 Oct;10(5):431–438. doi: 10.1007/BF01221634. [DOI] [PubMed] [Google Scholar]
  18. Malaisse-Lagae F., Sener A., Garcia-Morales P., Valverde I., Malaisse W. J. The stimulus-secretion coupling of amino acid-induced insulin release. Influence of a nonmetabolized analog of leucine on the metabolism of glutamine in pancreatic islets. J Biol Chem. 1982 Apr 10;257(7):3754–3758. [PubMed] [Google Scholar]
  19. Malaisse W. J., Hutton J. C., Kawazu S., Herchuelz A., Valverde I., Sener A. The stimulus-secretion coupling of glucose-induced insulin release. XXXV. The links between metabolic and cationic events. Diabetologia. 1979 May;16(5):331–341. doi: 10.1007/BF01223623. [DOI] [PubMed] [Google Scholar]
  20. Malaisse W. J., Malaisse-Lagae F., Sener A. The stimulus-secretion coupling of glucose-induced insulin release: effect of aminooxyacetate upon nutrient-stimulated insulin secretion. Endocrinology. 1982 Aug;111(2):392–397. doi: 10.1210/endo-111-2-392. [DOI] [PubMed] [Google Scholar]
  21. Malaisse W. J., Sener A., Carpinelli A. R., Anjaneyulu K., Lebrun P., Herchuelz A., Christophe J. The stimulus-secretion coupling of glucose-induced insulin release. XLVI. Physiological role of L-glutamine as a fuel for pancreatic islets. Mol Cell Endocrinol. 1980 Nov;20(2):171–189. doi: 10.1016/0303-7207(80)90080-5. [DOI] [PubMed] [Google Scholar]
  22. Malaisse W. J., Sener A., Herchuelz A., Hutton J. C. Insulin release: the fuel hypothesis. Metabolism. 1979 Apr;28(4):373–386. doi: 10.1016/0026-0495(79)90111-2. [DOI] [PubMed] [Google Scholar]
  23. Mitchell P. Vectorial chemistry and the molecular mechanics of chemiosmotic coupling: power transmission by proticity. Biochem Soc Trans. 1976;4(3):399–430. doi: 10.1042/bst0040399. [DOI] [PubMed] [Google Scholar]
  24. Panten U., Biermann J., Graen W. Recognition of insulin-releasing fuels by pancreatic B-cells: alpha-ketoisocaproic acid is an appropriate model compound to study the role of B-cell metabolism. Mol Pharmacol. 1981 Jul;20(1):76–82. [PubMed] [Google Scholar]
  25. Panten U., Christians J. Effect of 2-endo-aminonorbornane-2-carboxylic acid upon insulin secretion and fluorescence of reduced pyridine nucleotides of isolated perifused pancreatic islets. Naunyn Schmiedebergs Arch Pharmacol. 1973;276(1):55–62. doi: 10.1007/BF00500778. [DOI] [PubMed] [Google Scholar]
  26. Panten U. Effects of alpha-ketomonocarboxylic acids upon insulin secretion and metabolism of isolated pancreatic islets. Naunyn Schmiedebergs Arch Pharmacol. 1975;291(4):405–420. doi: 10.1007/BF00501798. [DOI] [PubMed] [Google Scholar]
  27. Panten U., Holze S., Lenzen S. Changes of function and metabolism of the pancreatic B-cell caused by amino acids and related compounds. Horm Metab Res Suppl. 1980;Suppl 10:27–30. [PubMed] [Google Scholar]
  28. Panten U., Ishida H., Schauder P., Frerichs H., Hasselblatt A. A versatile microperifusion system. Anal Biochem. 1977 Oct;82(2):317–326. doi: 10.1016/0003-2697(77)90167-1. [DOI] [PubMed] [Google Scholar]
  29. Panten U., Klein H. O2 consumption by isolated pancreatic islets, as measured in a microincubation system with a Clark-type electrode. Endocrinology. 1982 Nov;111(5):1595–1600. doi: 10.1210/endo-111-5-1595. [DOI] [PubMed] [Google Scholar]
  30. Panten U., Langer J. Mechanism of 3-phenylpyruvate-induced insulin release from isolated pancreatic islets. Biochem J. 1981 Aug 15;198(2):353–356. doi: 10.1042/bj1980353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sener A., Malaisse-Lagae F., Malaisse W. J. Stimulation of pancreatic islet metabolism and insulin release by a nonmetabolizable amino acid. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5460–5464. doi: 10.1073/pnas.78.9.5460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sener A., Malaisse W. J. L-leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase. Nature. 1980 Nov 13;288(5787):187–189. doi: 10.1038/288187a0. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES