Biomaterial Database

Short-term metabolic and haemodynamic effects of GR79236 in normal and fructose-fed rats. 1997

X Qu, and G Cooney, and R Donnelly

Department of Pharmacology, University of Sydney, Australia.

The adenosine (A1) receptor agonist, GR79236 (N-[(1S,trans)-2-hydroxycyclopentyl]adenosine), inhibits catecholamine-induced lipolysis in vitro, but the short-term metabolic and haemodynamic effects have not been previously reported in the fructose fed model of insulin resistance, dyslipidaemia and hypertension. This study reports the effects of GR79236 (1 mg/kg/day for 8 days) on nonesterified free fatty acid and triglyceride metabolism, oral and i.v. glucose tolerance, blood pressure and heart rate, and insulin sensitivity, in normal rats and rats fed a fructose-enriched diet. In normal rats, GR79236 significantly reduced fasting glucose (25%), free fatty acid (50%) and triglyceride (55%) concentrations, and improved glucose tolerance (AUC[glu] 21.2 +/- 1.3 vs. 16.5 +/- 1.1 mmol h/l, p < 0.05). Fructose feeding induced a state of insulin resistance and dyslipidaemia, as shown by an increase in steady-state plasma glucose levels (7.1 vs. 6.1 mmol/l), impaired i.v. glucose tolerance and a 3-fold rise in fasting triglyceride levels; fructose-fed rats also developed a significant increase in blood pressure. GR79236 ameliorated the effects of fructose feeding on fatty acid and triglyceride levels, and blood pressure, and improved i.v. glucose tolerance in fructose-fed rats. The hypotriglyceridaemic effect was due to a reduction in triglyceride secretion rate (17.3 +/- 1.7 vs. 30.2 +/- 1.1). Thus, in normal rats and in a dietary-induced rodent model of insulin resistance, dyslipidaemia and hypertension, GR79236 has lipid-lowering and glucose-lowering activity, as well as haemodynamic effects, which are potentially useful for treating both the metabolic and haemodynamic features of insulin resistance and NIDDM in humans.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007333	Insulin Resistance	Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.	Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D008297	Male		Males
D001786	Blood Glucose	Glucose in blood.	Blood Sugar,Glucose, Blood,Sugar, Blood
D001794	Blood Pressure	PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.	Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D005227	Fatty Acids	Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)	Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D005632	Fructose	A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding.	Levulose,Apir Levulosa,Fleboplast Levulosa,Levulosa,Levulosa Baxter,Levulosa Braun,Levulosa Grifols,Levulosa Ibys,Levulosa Ife,Levulosa Mein,Levulosado Bieffe Medit,Levulosado Braun,Levulosado Vitulia,Plast Apyr Levulosa Mein,Levulosa, Apir,Levulosa, Fleboplast
D005951	Glucose Tolerance Test	A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).	Intravenous Glucose Tolerance,Intravenous Glucose Tolerance Test,OGTT,Oral Glucose Tolerance,Oral Glucose Tolerance Test,Glucose Tolerance Tests,Glucose Tolerance, Oral
D006339	Heart Rate	The number of times the HEART VENTRICLES contract per unit of time, usually per minute.	Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000241	Adenosine	A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.	Adenocard,Adenoscan