Abstract
A continuous-flow centrifuge was used to infuse sodium salts of oleic, linoleic, lauric, or palmitic acid into the pancreatic artery of anesthetized dogs. In these regional perfusion studies there was no increase in FFA levels in the general circulation. Elevation of pancreatic FFA levels produced an immediate increase in pancreatic venous immunoreactive insulin (IRI). After 10 min of FFA infusion. IRI levels declined somewhat from the initial peak response but soon rose again to high levels which were then sustained until the infusion was terminated. All four long-chain FFA tested produced a similar biphasic IRI response. Clearcut increases in IRI were associated with absolute FFA levels (measured in pancreaticoduodenal venous plasma) as low as 0.6-0.8 μeq/ml and with increments over basal levels of as little as 0.4-0.5 μeq/ml. At higher levels of FFA, absolute IRI levels in the pancreatic venous effluent exceeded 1,000 μU/ml in some experiments and 5- to 10-fold increases over basal values were observed.
These studies indicate that long-chain FFA, in physiological concentrations, can markedly stimulate insulin secretion by a direct effect on the pancreas. The results lend support to the concept of insulin as a hormone that is importantly involved in regulating the metabolism of all three principal classes of metabolic substrates and whose release is in turn regulated by all of them. The relative importance and precise nature of its physiologic role in the regulation of lipolysis, lipid deposition, and ketone body formation remains to be established.
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- Clarke R. S., Johnston H., Sheridan B. The influence of anaesthesia and surgery on plasma cortisol, insulin and free fatty acids. Br J Anaesth. 1970 Apr;42(4):295–299. doi: 10.1093/bja/42.4.295. [DOI] [PubMed] [Google Scholar]
- Crespin S. R., Greenough W. B., 3rd, Steinberg D. Stimulation of insulin secretion by infusion of free fatty acids. J Clin Invest. 1969 Oct;48(10):1934–1943. doi: 10.1172/JCI106160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Curry D. L., Bennett L. L., Grodsky G. M. Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology. 1968 Sep;83(3):572–584. doi: 10.1210/endo-83-3-572. [DOI] [PubMed] [Google Scholar]
- Goetz F. C., Maney J. W., Greenberg B. Z. The regulation of insulin secretion: effects of the infusion of glucose, ribose, and other sugars into the portal veins of dogs. J Lab Clin Med. 1967 Apr;69(4):537–557. [PubMed] [Google Scholar]
- Greenough W. B., 3rd, Crespin S. R., Steinberg D. Infusion of long-chain fatty acid anions by continuous-flow centrifugation. J Clin Invest. 1969 Oct;48(10):1923–1933. doi: 10.1172/JCI106159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lerner R. L., Porte D., Jr Uniphasic insulin responses to secretin stimulation in man. J Clin Invest. 1970 Dec;49(12):2276–2280. doi: 10.1172/JCI106447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MADISON L. L., MEBANE D., UNGER R. H., LOCHNER A. THE HYPOGLYCEMIC ACTION OF KETONES. II. EVIDENCE FOR A STIMULATORY FEEDBACK OF KETONES ON THE PANCREATIC BETA CELLS. J Clin Invest. 1964 Mar;43:408–415. doi: 10.1172/JCI104925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malaisse W. J., Malaisse-Lagae F. Stimulation of insulin secretion by noncarbohydrate metabolites. J Lab Clin Med. 1968 Sep;72(3):438–448. [PubMed] [Google Scholar]
- Matschinsky F. M., Ellerman J. E., Krzanowski J., Kotler-Brajtburg J., Landgraf R., Fertel R. The dual function of glucose in islets of Langerhans. J Biol Chem. 1971 Feb 25;246(4):1007–1011. [PubMed] [Google Scholar]
- Montague W., Taylor K. W. Islet-cell metabolism during insulin release. Effects of glucose, citrate, octanoate, tolbutamide, glucagon and theophylline. Biochem J. 1969 Nov;115(2):257–262. doi: 10.1042/bj1150257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montague W., Taylor K. W. Regulation of insulin secretion by short chain fatty acids. Nature. 1968 Mar 2;217(5131):853–853. doi: 10.1038/217853a0. [DOI] [PubMed] [Google Scholar]
- Ohneda A., Parada E., Eisentraut A. M., Unger R. H. Characterization of response of circulating glucagon to intraduodenal and intravenous administration of amino acids. J Clin Invest. 1968 Oct;47(10):2305–2322. doi: 10.1172/JCI105916. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pi-Sunyer F., Campbell R. G., Hashim S. A. Experimentally induced hyperketonemia and insulin secretion in the dog. Metabolism. 1970 Apr;19(4):263–270. doi: 10.1016/0026-0495(70)90124-1. [DOI] [PubMed] [Google Scholar]
- Porte D., Jr, Bagdade J. D. Human insulin secretion: as integrated approach. Annu Rev Med. 1970;21:219–240. doi: 10.1146/annurev.me.21.020170.001251. [DOI] [PubMed] [Google Scholar]
- Renold A. E. Insulin biosynthesis and secretion--a still unsettled topic. N Engl J Med. 1970 Jan 22;282(4):173–182. doi: 10.1056/NEJM197001222820401. [DOI] [PubMed] [Google Scholar]
- Sanbar S. S., Evans J. R., Lin B., Hetenyi G., Jr Further studies on the effect of octanoate on glucose metabolism in dogs. Can J Physiol Pharmacol. 1967 Jan;45(1):29–38. doi: 10.1139/y67-003. [DOI] [PubMed] [Google Scholar]
- Sanbar S. S., Martin J. M. Stimulation by octanoate of insulin release from isolated rat pancreas. Metabolism. 1967 May;16(5):482–484. doi: 10.1016/0026-0495(67)90140-0. [DOI] [PubMed] [Google Scholar]
- Schalch D. S., Kipnis D. M. Abnormalities in carbohydrate tolerance associated with elevated plasma nonesterified fatty acids. J Clin Invest. 1965 Dec;44(12):2010–2020. doi: 10.1172/JCI105308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seyffert W. A., Jr, Madison L. L. Physiologic effects of metabolic fuels on carbohydrate metabolism. I. Acute effect of elevation of plasma free fatty acids on hepatic glucose output, peripheral glucose utilization, serum insulin, and plasma glucagon levels. Diabetes. 1967 Nov;16(11):765–776. doi: 10.2337/diab.16.11.765. [DOI] [PubMed] [Google Scholar]
- Unger R. H., Ketterer H., Dupré J., Eisentraut A. M. The effects of secretin, pancreozymin, and gastrin on insulin and glucagon secretion in anesthetized dogs. J Clin Invest. 1967 Apr;46(4):630–645. doi: 10.1172/JCI105565. [DOI] [PMC free article] [PubMed] [Google Scholar]