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Insulinotropic effects of certain blood metabolites in domestic sheep Ross, James Pelter


Blood propionate, butyrate, glucose, acetoacetate, and β-hydroxybutyrate were studied to determine if these metabolites have a role in the release of insulin from the pancreatic islets in domestic sheep. Since methods previously available for the measurement of plasma propionate and butyrate levels had a number of disadvantages, an improved method for the determination of blood volatile fatty acids was devised. A study was conducted to determine if blood volatile fatty acids and glucose are related to plasma insulin in sheep consuming different feeds. Postprandial changes in the concentrations of plasma volatile fatty acids, glucose and insulin were measured at 2 hour intervals in mature wethers fed barley, hay, or an equal mixture of barley and hay. The plasma constituents which showed an increase after feeding were insulin, glucose, and propionate for sheep fed barley; glucose, propionate, acetate, and isobutyrate for sheep fed hay; and glucose, acetate, propionate, butyrate and insulin for sheep fed barley and hay. Simple and multiple regression analyses were carried out relating plasma glucose and volatile fatty acids to plasma insulin within each dietary regime. These results indicated that butyrate and isobutyrate were the most important blood volatile fatty acids with respect to their relationship to plasma insulin levels in this study. A study of diurnal variation in plasma insulin, volatile fatty acids, and glucose levels in lactating ewes revealed a similar pattern of diurnal variation for glucose, acetate and propionate. Whereas these metabolites had a single maximum at 5 pm. and a minimum at 8 am, the plasma butyrate level appeared to reach a maximum at about 11 am as well as at 5 pm. The plasma insulin values appeared somewhat unreliable as indicated by the large variation in the data. The pattern of diurnal variation in these blood metabolites is discussed in relation to the regulation of insulin secretion. The relationship between plasma glucose and insulin levels in ad libitum fed and in prefasted-refed suckling lambs was determined. The degree of correlation varied considerably depending upon the experimental condition. The relevance of a statistically significant relationship between plasma insulin and a blood metabolite is discussed in relation to the regulatory role of plasma metabolites in the secretion of insulin. By experimentally altering the individual plasma propionate, butyrate and glucose levels within the estimated physiological range and measuring the corresponding plasma insulin levels, it was anticipated that the relative importance of each of these metabolites in the regulation of insulin secretion could be assessed. A phlorizin infusion to fed wethers caused a significant decrease in plasma glucose and insulin levels. Infusing glucose so as to elevate plasma glucose levels gradually to about 100 mg/100 ml failed to elicit an insulin secretory response. Infusion of propionate and butyrate at rates sufficient to increase plasma levels considerably above the upper limit of the physiological range failed to elicit an insulin secretory response. Only when plasma butyrate levels were elevated above 175 µmole/liter was an insulin secretory response obtained. These results suggest that the increase in plasma insulin level that normally occurs in sheep following the ingestion of concentrate-type feeds is not mediated by butyrate, propionate or glucose. However, the normal level of plasma insulin in fed sheep, at least in part, appears to be maintained by the plasma glucose level. β-hydroxybutyrate and acetoacetate were studied to determine if physiological increases in the blood level of these metabolites would affect the level of plasma insulin. Only acetoacetate had an insulinotropic action when injected to fasted non-pregnant ewes. The injected acetoacetate appeared to be rapidly reduced within the blood to β-hydroxybutyrate. The results are discussed in relation to an etiologic role of acetoacetate in rurninant ketosis.

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