Changes In Plasma Glucose Concentrations Research Articles

Comparison of the hyperglycaemic and glycogenolytic responses to catecholamines with those to stimulation of the hepatic sympathetic innervation in the dog.

1. The effects of stimulation of the splanchnic innervation to the adrenal medullae, in dogs with cut hepatic nerves, were compared with those obtained previously in response to splanchnic and hepatic nerve stimulation in adrenalectomized dogs.2. Maximal stimulation of both adrenal medullae via the splanchnic innervation (20 c/s for 9 min), in dogs with cut hepatic nerves, produced closely similar hyperglycaemic and glycogenolytic responses to those obtained previously in adrenalectomized dogs with intact hepatic nerves.3. The rise in plasma glucose concentration in response to maximal stimulation of the adrenal medullae in dogs with intact hepatic nerves was found to be comparable to that which occurs in response to maximal stimulation of the hepatic sympathetic innervation alone. In contrast, the rise in haematocrit during maximal stimulation of the entire splanchnic innervation was substantially greater than that observed after removal of both adrenal glands.4. The output of adrenaline and noradrenaline from the left adrenal gland was determined during maximal stimulation of the left splanchnic nerve (20 c/s for 9 min). These results were then used to compute doses of the two amines which would reproduce the output of catecholamines from both glands under such conditions. The extent of the rise in mean plasma glucose concentration in response to these infusions was similar to that produced by maximal stimulation of both adrenal glands, but the duration of hyperglycaemia and depletion of liver glycogen were significantly less.5. Stimulation of the splanchnic innervation was found to produce an initial ;surge' in the release of catecholamines from the adrenal medullae, followed by a rapid decline in output when stimulation was continued for longer than 30 sec. Evidence was obtained which showed that this pattern of release is well suited to produce rapid mobilization of liver glycogen.6. Comparable changes in plasma glucose concentration occurred in response to stimulation of either the adrenal medullae or the sympathetic innervation to the liver at low frequency (2.0 c/s for 5 min). Stimulation of both pathways simultaneously, at the same frequency, produced smaller responses.7. Intramesenteric infusions of noradrenaline at 1.0 mug.kg(-1) min(-1) for 5 min produced comparable changes in plasma glucose concentration to those observed during stimulation of either pathway alone at low frequency. The mean plasma noradrenaline concentration of portal blood was raised by between 92 and 105 ng/ml. during these infusions.8. It is concluded that stimulation of either the splanchnic innervation to the liver, or of both adrenal medullae, at high frequency (20 c/s for 9 min) represents a supramaximal stimulus for hepatic glycogenolysis. Comparison of the responses to stimulation at low frequency (2.0 c/s for 5 min) suggests that the hepatic glycogenolytic mechanism is equally sensitive to stimulation via either route in this species.

The hyperglycaemic response to stimulation of the hepatic sympathetic innervation in adrenalectomized cats and dogs.

1. The extent to which the hyperglaemic and glycogenolytic responses to splanchnic nerve stimulation depend upon the integrity of the hepatic innervation has been investigated in adrenalectomized dogs and cats.2. In both species maximal stimulation of the hepatic nerves (20 c/s) produced changes in plasma glucose concentration comparable to those which have been found to occur in response to bilateral splanchnic nerve stimulation at the same frequency. Furthermore, the hyperglycaemic response to splanchnic nerve stimulation was very substantially reduced by section of the hepatic nerves, whereas the associated changes in haematocrit and mean aortic blood pressure were not significantly altered.3. Comparison of the changes in plasma glucose concentration in response to splanchnic or hepatic nerve stimulation at relatively low frequencies (1.0-2.0 c/s) showed that stimulation of either nerve produced closely similar responses in adrenalectomized animals of both species.4. In adrenalectomized dogs maximal stimulation of the hepatic nerves (20 c/s) for shorter periods (30 sec) caused a significant rise in plasma glucose concentration whereas total occlusion of the portal vein for the same period in the same animals produced no statistically significant hyperglycaemic effect.5. Maximal stimulation of the hepatic nerves (20 c/s) caused a rapid rise in plasma glucose concentration in hypoglycaemic adrenalectomized cats pretreated with a large dose of insulin (4 u./kg body wt.).6. It is concluded that the hyperglycaemic response to stimulation of the peripheral ends of the splanchnic nerves in adrenalectomized dogs and cats is directly dependent upon activation of sympathetic efferent fibres to the liver.

The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves, sheep, dogs, cats and pigs

1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in calves, sheep, dogs, cats and pigs after removal of both adrenal glands.2. Stimulation of both splanchnic nerves produced comparable hyperglycaemic and glycogenolytic effects in sheep, dogs and cats; the mean liver glycogen concentration was reduced by between 7.0 and 10.5 mg/g, five min after stimulation was discontinued, at which time the mean plasma glucose concentration had risen by between 126 and 137 mg/100 ml.3. In five 3-5 week-old calves which were tested under identical conditions the mean liver glycogen concentration was reduced by 13.3 +/- 1.9 mg/g and the plasma glucose concentration raised by 216 +/- 1.9 mg/100 ml., 5 min after stimulation was terminated.4. In pigs, stimulation of both splanchnic nerves invariably produced a rise in the plasma glucose concentration, even when the concentration of glycogen in the liver was less than 5 mg/g before stimulation. The response was, nevertheless, considerably smaller in these animals than in any of the other species investigated.5. Splanchnic nerve stimulation also caused a rise in mean aortic blood pressure and blood haematocrit during the period of stimulation; changes of approximately the same order of magnitude were encountered in all five species.6. Dogs were found to resemble calves in that the hyperglycaemic response to stimulation of a single splanchnic nerve did not differ significantly from that obtained when both were stimulated simultaneously; furthermore, either nerve was found to be equally effective.7. In cats the change in plasma glucose concentration in response to stimulation of a single splanchnic nerve was always less than that which occurred in response to bilateral stimulation although comparable changes in blood haematocrit occurred in both groups of animals.8. It is concluded that stimulation of the splanchnic nerves causes break-down of glycogen in the livers of various unrelated species of adult animals but that the magnitude of the hyperglycaemic response in the young calf provides further evidence of the importance of the sympathetic system in the control of metabolism in the young animal.

Control of pancreatic glucagon secretion by glucose.

Recent questions concerning the role of glucagon as a hormone of “glucose need” prompted this evaluation of glucose-glucagon relationships. To obviate certain problems relating to the sensitivity and specificity of the glucagon radioimmunoassay of peripheral venous plasma, glucagon was assayed in pancreatic venous effluent plasma obtained from conscious dogs with indwelling catheters in the pancreaticoduodenal vein. The effect of change in glucose concentration upon the pancreaticoduodenal vein glucagon concentration was determined. Insulin induced hypoglycemia was uniformly associated with a rise in pancreaticoduodenal vein glucagon concentration to a peak of 5.7 mμg./ml. at thirty minutes. The hyperglucagonemia continued intermittently during the hypoglycemic period but fell promptly during hyperglycemia induced by rapid injection of glucose. Hyperglycemia, induced in fifteen dogs by glucose infusion, was accompanied by a decline of glucagon from 2.7 to 1.8 mμg./ml. Cataglycemia, induced by rapid termination of a glucose infusion, produced a rise of glucagon in three of six dogs. Stimulation of glucagon secretion by hyperaminoacidemia was blocked by hyperglycemia induced by glucose infusion. The effect of starvation upon twenty-four-hour secretion of glucagon could not be determined in these studies. Wide variations in pancreaticoduodenal vein glucagon concentration made meaningful comparison of day-to-day changes impossible. A statistically significant negative correlation was observed between rapidly induced change in plasma glucose concentration and change in pancreaticoduodenal vein glucagon levels. The findings are compatible with the view that glucagon is a hormone of glucose need, which probably functions in the moment-to-moment regulation of blood glucose homeostasis and the maintenance of the so-called “normal” blood glucose limits.

Metabolism of plasma glucose and lipids following diazoxide administration in dogs

Acute effects of a single intravenous injection of diazoxide on plasma glucose and lipid metabolism were investigated in 12 healthy, anesthetized dogs, each serving as its own control. The dose of diazoxide/Kg. body weight was 20 mg. in 8 dogs and 15 mg. in 4 dogs. Glucose metabolism was determined in 7 dogs using 4 successive measured injections of tracer glucose-U-C 14, and turnover rates of plasma FFA were estimated in 3 dogs using a constant intravenous infusion of trace amounts of both palmitic acid-9, 10-H 3 and linoleic acid-1-C 14, complexed with albumin. The larger dose of diazoxide evoked in all 8 dogs prompt increments in both plasma glucose and FFA concentrations, with mean ± 1 S.E. maximal increases above control values of 106 ± 30 mg. 100 ml. and 920 ± 174 μEq./L., respectively. On the other hand, plasma triglyceride and cholesterol concentrations did not change significantly for 3 3 4 hours after diazoxide administration. In keeping with the change in plasma glucose concentration, intermixing glucose mass, determined in 3 of the 8 dogs, showed an average maximal increase of 62 per cent above control after diazoxide. Rate of glucose appearance (primarily hepatic output) was increased by 42 per cent above control immediately after diazoxide but returned to control values 1 1 4 hours later. Interestingly enough, rate of glucose disappearance (tissue uptake) was not altered significantly by diazoxide despite the marked increase in plasma concentration and intermixing mass of glucose. The smaller dose of diazoxide produced in the remaining 4 dogs less pronounced alterations than the above, but the trend was similar. During simultaneous infusion of labeled palmitate and linoleate in 3 dogs, concentrations of H 3 and C 14 radio-activities of plasma FFA were slightly increased, but plasma FFA specific activities were decreased by diazoxide. Mean ± 1 S.E. turnover rates of plasma FFA during the control periods were 29.9 ± 2.4 and 27.3 ± 2.1 μEq./min. for H 3-FFA and C 14-FFA, respectively, while corresponding rates after diazoxide were 101.9 ± 29.5 and 79.2 ± 19.6 μEq./min. Finally, despite the fall in specific activities of plasma FFA which presumably would likewise affect the hepatic FFA pools that provide precursors for triglyceride synthesis, the rates of incorporation of H 3 and C 14 labeled FFA into plasma triglyceride were increased. In conclusion, diazoxide induces hyperglycemia in dogs as a result of increased hepatic glucose output and relative inhibition of glucose utilization by tissues, and it raises plasma FFA concentration by enhancing the influx of FFA into plasma.

Plasma growth hormone after arginine infusion. Clinical experiences.

INFUSION of arginine monochloride is followed by a rise in the plasma concentration of human growth hormone in normal subjects.1 , 2 The infusion is accompanied by modest changes in plasma glucose concentration. The subjects exhibit no discomfort, and in our experience, the procedure has been entirely without untoward effects. It occurred to us at the time of our initial report of arginine-initiated release of human growth hormone that this observation had potential clinical application.1 After the development of a sensitive immunoassay for measurement of this hormone in plasma by Berson and his colleagues3 the definitive demonstration of its deficiency became possible. . . .

Further studies on the effect of octanoate on glucose metabolism in dogs.

Studies were carried out in anesthetized dogs to elucidate the mechanism of action of octanoate on glucose metabolism.Octanoate infusion in intact healthy dogs significantly decreased plasma glucose concentration, and in four out of seven dogs it raised plasma insulin concentration in peripheral blood. In contrast, intravenous administration of octanoate in four totally pancreatectomized dogs produced only small changes in plasma glucose concentration. These data suggest that the hypoglycemic action of octanoate may be mediated by increased secretion of insulin.The mean k value ([Formula: see text] of plasma glucose concentration) of intravenous glucose tolerance tests was significantly higher (2.38/minute) in healthy dogs that received an infusion of octanoate than in dogs that did not (1.2/minute). Octanoate also produced in healthy dogs greater increases in plasma insulin concentrations of peripheral blood during the tolerance tests. Furthermore, when delivered during a continuous intravenous administration of glucose (about 8 mg/kg per minute), octanoate infusion had no effect on either plasma glucose concentration or the rate of disappearance of glucose-U-14C from plasma to tissues. These findings indicate that octanoate does not impair glucose utilization in healthy dogs but actually improves tolerance of an intravenous glucose load, probably by stimulating greater release of insulin. These findings in vivo are discussed in the light of opposite effects of octanoate in vitro, to be described elsewhere, on glucose metabolism in the isolated heart and fat pad of rats.

Growth hormone-insulin interaction. Fact and speculation.

The metabolic effects of human growth hormone may be segregated into two classes which can be termed “insulinlike” (or “anabolic”) and “contra-insulin” (or “diabetogenic”). It is proposed that the “anabolic” actions of HGH are optimized by the presence of insulin, whereas the “diabetogenic” actions are dominant in the absence of insulin. In line with this notion, the sequential release of insulin and of HGH which follows protein ingestion, or aminoacid infusion may serve to route aminoacid toward protein, while buffering changes in plasma glucose concentration.

Relationship of Ketone Body Metabolism and Carbohydrate Utilization to Fat Mobilization in the Ruminant

A significant decrease in plasma non-esterified fatty acid (NEFA) level occurred during intravenous administration of sodium β-hydroxybutyrate to goats previously fasted or fasted and phlorizinized. No significant change in plasma glucose concentration was observed during the infusion in either metabolic state. A depression in plasma NEFA level of lower magnitude was also noted during infusion of β-hydroxybutyrate to alloxan-diabetic goats. A direct feedback effect of ketone bodies on fat mobilization is implicated, although the presence of insulin may be necessary for maximum suppression of NEFA release.

Insulin response to ingested protein in diabetes.

The ingestion of protein by normal human subjects has been shown recently to represent a stimulus to the secretion of insulin. This response is probably related to the postprandial rise in plasma amino acid concentration. Since disordered protein synthesis may contribute to the pathogenesis of diabetes and its complications, the insulin response to ingested protein (casein or gelatin, 50-100 gm.) was compared in twenty-eight normals and ten maturity-onset diabetics. Insulin response (microunits-minutes, μU.-min.) was considered to be the area included by that portion of the plasma insulin response curve above projected basal insulin secretion. Following protein ingestion the diabetics showed a mean insulin response (± S.E.M.) of 3,425 ± 367 μU.-min., compared with 1,005 ± 136 in the normals, a 3.4-fold difference (p < 0.01). In neither group were there significant or consistent changes in plasma glucose concentration. The fall in free fatty acids was comparable and no difference was seen in the plasma amino acid nitrogen curves. These data indicate that the insulin response to ingested protein is excessive in diabetes. The mechanism of the hyperresponse would seem to lie within the beta cell since no abnormality of the presumed amino acid stimulus was demonstrated.