Effects of infusion of octanoate on glucose concentration in plasma and the rates of glucose production and utilization in dogs

Sanbar, Shafeek S.; Hetenyi, G; Forbath, N.; Evans, John R.

doi:10.1016/s0026-0495(65)80013-0

Cited by 44 publications

(10 citation statements)

References 30 publications

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“…49 In the present studies, significant inhibition (25 per cent) occurred at 20 min. (table 1) by which time mean hepatic glucose output had fallen 16.2 mg. per minute without any change in arterial glucose concentration.…”

Section: Discussionsupporting

confidence: 51%

“…Stimulation of insulin secretion by (3-hydroxybutyric acid and acetoacetic acid previously reported by Madison et al 50 has recently been confirmed in children. 51 In the studies of Sanbar et al 49 the role of octanoate per se on the pancreatic beta cell could not be separated from the action of ketones. In the present studies, increased concentrations of plasma free fatty acids produced a significant increase in plasma insulin unassociated with any concomitant elevation of arterial ketone levels (tables 3 and 5).…”

Section: Discussionmentioning

confidence: 99%

“…The data from the present studies can be added to the increasing evidence 25 -39 " 41 supporting a direct effect of insulin on the liver; additional support comes from the recent studies of Exton and associates 42 confirming the findings of Mortimore, who showed a direct effect of insulin on the hepatic release of glucose in the perfused rat liver preparation. 40 Elevation of the plasma concentration of octanoate, a medium chain fatty acid, also reduces hepatic glucose production in dogs/ 9 Sanbar et al 49 ascribed this effect to increased insulin secretion in part secondary to the rapid hepatic conversion of octanoate to ketone bodies. Stimulation of insulin secretion by (3-hydroxybutyric acid and acetoacetic acid previously reported by Madison et al 50 has recently been confirmed in children.…”

Section: Discussionmentioning

confidence: 99%

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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

Seyffert¹,

Madison²

1967

Diabetes

151

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The in vivo effects of acute changes in the concentration of plasma free fatty acids on hepatic glucose output and peripheral glucose utilization were defined in thirteen studies in dogs. Dogs with chronic end-to-side portacaval shunts were used thereby permitting not only measurement of hepatic rather than splanchnic glucose output but also the rate of peripheral glucose utilization. In eighteen additional studies the effect of acute elevations of plasma free fatty acids on serum insulin, plasma glucagon, blood ketones and alpha-amino nitrogen was determined. The quantitative and qualitative changes in plasma free fatty acids which occur during starvation were simulated by the intravenous administration of a cottonseed oil emulsion plus heparin. The acute elevation of plasma free fatty acids produced a 37 per cent decrease in hepatic glucose output and a 30 per cent inhibition of peripheral glucose utilization. This decrease in hepatic glucose output was the consequence both of a significant increase in the secretion of insulin and a decrease in glucagon secretion. These changes in hormonal milieu which attended the increase in plasma free fatty acids could not be ascribed to changes in blood ketones or amino acids since the concentrations of these substances remained unchanged. These data suggest that this feedback of free fatty acids on secretion of insulin and glucagon plays an important physiologic role during starvation in the safe transition from carbohydrate to fat metabolism without the danger of progressive ketoacidosis. it is likely that during starvation plasma free fatty acids contribute to the control and maintenance of a low but vital concentration of plasma insulin. DIABETES 16: 765-76, November, 1967. During prolonged starvation, plasma free fatty acids (FFA) rise to a new elevated steady state level. 1 " 3 Concomitant with this rise in FFA is the well-known impairment in glucose tolerance, referred to as starvation diabetes. 4 " 5 Similarly, a diminution in glucose tolerance

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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

Seyffert¹,

Madison²

1967

Diabetes

151

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“…as is expressed by Black et al [2], in lactaling cows and a pancreatic action of insulin release as is well known in L-leucine [18] and was suspected [14] and now demonstrated [15] in fatty acids. The intensity of each of these effects can be different in different species and, in each of these in different metabolic conditions and thus the different final effects may become understandable and, in this case, the hyper glycemic action reported here.…”

Section: Resultsmentioning

confidence: 89%

Leucine-Induced Hyperglycemia in the Goat

Sobrinho‐Simöes¹,

Hipólito-Reis²

1967

Pharmacology

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“…Experiments in vivo have indicated that long-chain fatty acids (Crespin et al 1969(Crespin et al , 1973Seyffert & Madison 1967), octanoic acid (Linscheer et al 1967;Sanbar et al 1965 (Hawkins et al 1971;Jenkins et al 1970;Madison et al 1964;Mebane & Madison 1964;Metzger et al 1973;Pi-Sunyer et al 1970) have a hypoglycaemic effect, which in general has been attributed to an enhancement of insulin release, although other explanations may also be valid (Balasse et al 1967; Balasse & Ooms 1968;Fajans et al 1964;Senior & Loridan 1968). Furthermore, acute ex¬ periments in vitro have shown that both fatty acids (Berne 1975a;Cole & Logothetopoulos 1974;Ed¬ wards et al 1972) and ketone bodies (Berne 1975a) are oxidized by the B-cell.…”

mentioning

confidence: 99%

Effects of octanoate and ketone bodies on the structure and function of isolated pancreatic islets in tissue culture

Borg

1981

Acta Endocrinologica

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To study the effects of fatty acids and ketone bodies on both insulin release and lasting changes in ultrastructure and function of the pancreatic B-cell, isolated mouse islets were cultured for one week in the presence of either octanoate, acetoacetate or 3-hydroxybutyrate. The glucose concentration of the unsupplemented culture medium was 3.3 mmol/l and islets cultured in this medium were used as controls. It was found that octanoate stimulated insulin accumulation in the culture medium, decreased the islet insulin content and also effected a degranulation of the islet B-cells. Although there was no significant change in the total mitochondrial volume of the octanoate cultured islets, the activity of the mitochondrial marker enzyme L-3\x=req-\ hydroxyacyl-CoA-dehydrogenase was decreased. In short-term incubations performed after culture with octanoate, there was an increased rate of islet protein biosynthesis, which seemed to be independent of a glucose challenge. After culture of islets with acetoacetate, morphometrical measurements indicated an increased islet cell size, but there appeared to be no further effects of this ketone body on the islet ultrastructure or function. 3-Hydroxybutyrate, however, increased both the insulin accumulation in the culture medium and the insulin content of the cultured islets. Apparently, the \g=b\-granule content of the islets exposed to 3-hydroxybutyrate also

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Effects of infusion of octanoate on glucose concentration in plasma and the rates of glucose production and utilization in dogs

Cited by 44 publications

References 30 publications

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

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

Leucine-Induced Hyperglycemia in the Goat

Effects of octanoate and ketone bodies on the structure and function of isolated pancreatic islets in tissue culture

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