Hyperglycemia In Normal Rats Research Articles

Acute effect of Bauhinia forficata on serum glucose levels in normal and alloxan-induced diabetic rats

Experimental diabetes was used to study the acute effect of the n-butanol fraction of Bauhinia forficata Link (Leguminosae) (BF) leaves on the serum glucose levels of rats. Body weight was measured on the day of diabetes induction and on the day of the experiment. Levels of glucose were determined at different doses and times following treatment with BF or with vehicle in normal, diabetic and hyperglycemic normal rats. Oral administration of n-BuOH fraction led to a significant blood glucose-lowering effect in normal and diabetic rats. However, in glucose-fed hyperglycemic normal rats, the maximum dose of this fraction failed to decrease blood glucose levels. The hypoglycemic effect was observed at doses of 500 and 600 mg/kg after 1 and 2 h treatment respectively, in normal rats. The maximum effect of BF was detected at 1 h with 800 mg/kg in diabetic animals and this profile was maintained for the next 3 h. Treatment of normal and alloxan-induced diabetic rats with BF decreased glucose levels, while this fraction was devoid of hypoglycemic effect in glucose-fed hyperglycemic normal rats.

Synthesis of two glucagon antagonists: receptor binding, adenylate cyclase, and effects on blood plasma glucose levels.

In diabetes mellitus, hyperglycemia is often associated with elevated levels of glucagon in the blood. This suggests that glucagon is a contributing factor in the metabolic abnormalities of diabetes mellitus. A glucagon-receptor antagonist would provide direct evidence for glucagon's role in diabetes mellitus. On the basis of careful consideration of conformational, amphiphilic, and structural factors, we have synthesized two new glucagon analogues with antagonist biological activities by using solid-phase methodology. These two new analogues, [Asp3,D-Phe4,Ser5,Lys17,18,Glu21]glucagon (2) and [D-Phe4,Tyr5,3,5-I2-Tyr10,Arg12,Lys17,18,G lu21]glucagon (3) had IC50 values 5.4% and 50% those of glucagon, respectively, and showed no measurable adenylate cyclase activity. When tested in normal rats, 2 lowered plasma glucose levels and suppressed glucagon-mediated hyperglycemia 105 +/- 8%, back to basal levels. Analogue 3, which lowered the basal adenylate cyclase activity in rat liver plasma membranes, increased plasma glucose levels at very high concentration in vivo and inhibited glucagon-mediated hyperglycemia in normal rats by 50%. However, neither of the new glucagon antagonists lowered the plasma glucose levels of diabetic animals. The data would suggest these new glucagon-receptor antagonists may have two actions: (a) in normal rats they can act as standard glucagon-receptor inhibitors of glucagon-mediated glycogenolysis; (b) in diabetic rats, however, because of the low levels of glycogen in the liver, the antagonists apparently have little or no antagonist effect or enhancement on glucagon-mediated glucose production.

Involvement of endogenous epinephrine in histamine-induced hyperinsulinemia and hypoglycemia in rats treated with islet-activating protein

Islet-activating protein (IAP), purified from the culture medium of Bordetella pertussis, was injected i.v. into rats at a dose of 5 μg/kg. While the injection of histamine caused hyperglycemia in normal rats, it caused marked hypoglycemia associated with hyperinsulinemia in IAP-treated rats. No hypoglycemia developed after histamine if the IAP-treated rats had been adrenodemedullated or injected with a β-adrenergic antagonist or with anti-insulin serum. Histamine-induced hyperinsulinemia in IAP-treated rats was also abolished by adrenodemedullation or a β-adrenergic antagonist. Ether anesthesia, which provokes the release of epinephrine from the adrenal medullae, mimicked the action of histamine in both normal and IAP-treated rats. Histamine did not influence insulin secretion when it was added directly to the incubation medium islets isolated from IAP-treated rats. It is concluded that epinephrine released from the adrenal medullae in response to histamine challenge enhances insulin secretion via the β-adrebergic receptors, thereby causing severe hypoglycemia in IAP-treated rats.

Absence of hyperglycemic effect of glucagon in the eviscerate rat.

SummaryEviscerated rats were given continuous intravenous injections of glucose. The intravenous injection of glucagon failed to affect the level of blood glucose in eviscerated rats but did cause hyperglycemia in normal rats.

Vago-Insulin and Sympathetico-Adrenal Systems, Their Mutual Relationship. II. Reaction to Cocaine and Bulbocapnine.

1. Subcutaneous injection of cocaine hydrochloride causes hyperglycemia in normal rats and hypoglycemia in adrenalectomized rats. If the vagi are sectioned subdiaphragmatically in the adrenalectomized rats, there is no significant change in blood sugar. If the vagi are cut subdiaphragmatically in normal animals, there is a greater increase in blood sugar than in animals with intact vagi. 2. Similar results are obtained with bulbocapnine phosphate. 3. These results are interpreted to mean that cocaine and bulbocapnine although acting quite differently on the somatic nervous system have a similar action on the autonomic system. They stimulate both the vago-insulin and the sympathetico-adrenal system. The effect on the latter predominates in the normal animal.