Literature on the effects of β-blockers on blood glucose is reviewed. Data are presented regarding the adrenergic influences on glucose regulation and the effects of β-blockade during hypo- and hyperglycemia in normal and diabetic individuals.
β-adrenergic stimulation enhances insulin and glucagon secretion, as well as glycogenosis, gluconeogenesis, and lipolysis. α-adrenergic stimulation inhibits insulin secretion and may inhibit glucagon secretion and enhance liver glycogenolysis. In nondiabetics, β-blockers represent minimal risk of affecting glucose control. In insulin-dependent diabetics, β-blockers can prolong, enhance, or alter the symptoms of hypoglycemia, while hyperglycemia appears to be the major risk in noninsulin-dependent diabetics. β-blockers can potentially increase blood glucose concentrations and antagonize the action of oral hypoglycemic drugs.
SMITHP.H., PORTED., ROBERTSONR.P.Neural regulation of the endocrine pancreas. In: PierlussiJ., ed. International symposium on the endocrine pancreas and diabetes.Amsterdam: Excerpta Medica, 1979: 64–95.
2.
CREYERP.E.Glucose counterregulation in man. Diabetes1981; 30: 261–4.
3.
RIZZAR.A., CREVERP.E., GERICHJ.E.Role of glucagon, catecholamines and growth hormone in human glucose counterregulation. J Clin Invest1919; 64: 62–71.
4.
PORTED.A receptor mechanism for the inhibition of insulin release by epinephrine in man. J Clin Invest1967; 46: 86–94.
5.
SAIBENEV., MARTINELLIG., VASCONIF., POZZAG.Clonidine effect on insulin secretion and lipolysis in man. Acta Diabetol Lat1978; 15: 192–7.
6.
POGASTAG., DUBECZE.Effect of propranolol on drug-induced and physiological glycogenosis in the liver. Arzneimittelforsch1979; 29: 1104–7.
7.
RIZZAR.A., CREYERP.E., HAYMONDM.W., GERICHJ.E.Adrenergic mechanisms for the effect of epinephrine on glucose production and clearance in man. J Clin Invest1980; 65: 682–9.
8.
RIZZAR.A., GERICHJ.E.Hypoglycemia: physiologic and pathophysiologic consideration. In: ServiceF.J., ed. Hypoglycemic disorders, pathogenesis, diagnosis, and treatment.Boston: GK Hall, 1983: 1–34.
9.
ROBERTSONR.P., PORTED.Adrenergic modulation of basal insulin secretion in man. Diabetes1973; 22: 1–8.
10.
PORTED.Beta adrenergic stimulation of insulin release in man. Diabetes1967; 16: 150–5.
11.
HARMSH.H., GOORENL., SPOELSTRAA.J.G., HESSEC., VERSCHOORL.Blockade of isoprenaline-induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol. Br J Clin Pharmacol1978; 5: 19–26.
12.
MASSARAF., FASSIOV., CAMANNIF., MOLINATTIG.M.Salbutamol-induced increase in plasma insulin in man. Horm Metab Res1975; 7: 94.
13.
KANETOA., MIKIE., KOSAKAK.Effect of beta and beta, adrenoreceptor stimulants infused intrapancreatically on glucagon and insulin secretion. Endocrinology1975; 97: 1166–73.
14.
LOUBATIERESA., MARIANIM.M., SORELG., SAVIL.The action of beta-adrenergic blocking and stimulating agents on insulin secretion. Characterization of the type of beta receptor. Diabetologia1971; 7: 127–32.
15.
PORTED., ROBERTSONR.P.Control of insulin secretion by catecholamines, stress, and the sympathetic nervous system. Fed Proc1973; 32: 1792–6.
16.
YOUNGJ.B., LANDSBERGL.Catecholamines and the regulation of hormonal secretion. Clin Endocrinol Metab1977; 6: 657–95.
17.
KOBAYASHIS., KOHEIH.Some metabolic actions of imidazoline sympathomimetics: hyperglycemia and lipid mobilization (abstract). Jap J Pharmacol1972; 22(suppl): 66.
18.
GERICHJ.E., LANGLOISM., NOACCOC., SCHNEIDERV., FORSHAMP.H.Adrenergic modulation of pancreatic glucagon secretion in man. J Clin Invest1974; 53: 1441–6.
19.
WALTERR.M., DUDLR.J., PALMERJ.P., ENSINCKJ.W.The effect of adrenergic blockade on the glucagon responses to starvation and hypoglycemia in man. J Clin Invest1974; 54: 1214–20.
20.
MASSARAF., CAMANNIF., MOLLINATTIG.Effect of propranolol on some adrenaline- and insulin-induced metabolic changes in man. Acta Diabetol Lat1975; 12: 41–51.
21.
RAPTISS.Effects of cardioselective and non-selective beta-adrenoreceptor blockade on glycogenolysis, lipolysis and growth hormone secretion. Br J Clin Pharmacol1982; 13: 419–20s.
22.
LAURIDSENU.B., CHRISTENSENN.J., LYNGSOEJ.Effects of nonselective and beta-1-selective blockade on glucose metabolism and hormone responses during insulin-induced hypoglycemia in normal man. J Clin Endocrinol Metab1983; 56: 876–82.
23.
KLEINBAUMJ., SHAMOONH.Effect of propranolol on delayed glucose recovery after insulin-induced hypoglycemia in normal and diabetic subjects. Diabetes Care1984; 7: 155–62.
24.
GREENBLATTD.J., KOCH-WESERJ.Adverse reactions to beta-adrenergic receptor blocking drugs: a report from the Boston Collaborative Drug Surveillance Program. Drugs1974; 7: 118–29.
25.
SELTZERH.S.Drug-induced hypoglycemia, a review based on 473 cases. Diabetes1972; 21: 955–66.
26.
MCMURTRYR.J.Propranolol, hypoglycemia and hypertensive crises (letter). Ann Intern Med1974; 80: 669–70.
27.
KOTLERM.N., BERMANL., RUBENSTEINA.H.Hypoglycemia precipitated by propranolol. Lancet1966; 2: 1389–90.
WELEDB.J., BALLJ., HOFELDTF.D.The hypoglycemic hazards of propranolol in diabetic patients: case reports. Milit Med1980; 145: 705–8.
30.
MACINTOSHT.F.Propranolol and hypoglycemia. Lancet1967; 1: 104–5.
31.
BELTONP., CARMODYM., DONOHOEJ.Propranolol associated hypoglycemia in non-diabetics. J Irish Med Assoc1980; 73: 173.
32.
ROTHD.A., MEADER.C.Hyperinsulinism-hypoglycemia in the post-gastrectomy patient. Diabetes1965; 14: 526–8.
33.
UUSITUPAM., AROA., PIETIKAINENM.Severe hypoglycemia caused by physical strain and pindolol therapy. Ann Clin Res1980; 12: 25–7.
34.
ROBERTSONR.P., PORTED.The glucose receptor. A defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor. J Clin Invest1973; 52: 870–6.
35.
LYNGSOEJ., LAURIDSENU.B., CHRISTENSENN.J.Effects of atenolol and propranolol on glucose metabolism and hormonal responses during insulin-induced hypoglycemia in normal man. Drugs1983; 25(suppl 2): 237–40.
36.
CERASIE., LUFTR., EFENDICS.Effect of beta adrenergic blocking agents on insulin response to glucose infusion in man. Acta Endocrinol1972; 69: 335–46.
37.
VEDINA., WILHELMSSONC., BJORNTORPP.Induction of diabetes and oral glucose tolerance tests during and after chronic beta-blockade. Acta Med Scand1975; 197(suppl 575): 37–40.
38.
HEDSTRANDH., ABERGH.Insulin response to intravenous glucose during long-term treatment with propranolol. Acta Med Scand1974; 196: 39–40.
39.
ABRAMSONE.A., ARKYR.A., WOEBERK.A.Effects of propranolol on the hormonal and metabolic responses to insulin-induced hypoglycemia. Lancet1966; 2: 1386–8.
40.
RYANJ.R., LACORTEW., MCMAHONF.G., MCMAHONJ.Response of diabetics treated with atenolol or propranolol to insulin-induced hypoglycemia. Drugs1983; 25(suppl 2): 256–7.
41.
DEACONS.P., KARUNANAYAKEA., BARNETTD.Acebutolol, atenolol, and propranolol and metabolic responses to acute hypoglycemia in diabetics. Br Med J1977; 2: 1255–7.
42.
SCHLUTERK.J., AELLIGW.H., PETERSENK.G., RIEBANDH.C., WEHRLIA., KERPL.The influence of beta-adrenoreceptor blocking drugs with and without intrinsic sympathomimetic activity on the hormonal responses to hypo- and hyperglycemia. Br J Clin Pharmacol1982; 13: 407–17s.
43.
OSTMANJ., ARNERP., HAGLUNDK., JUHLIN-DANNFELTA., NOWAKJ., WENNLUNDA.Effect of metoprolol and alprenolol on the metabolic, hormonal and hemodynamic response to insulin-induced hypoglycemia in hypertensive, insulin-dependent diabetics. Acta Med Scand1982; 211: 381–5.
LAGERI., BLOHMEG., SMITHU.Effect of cardioselective and non-select selective beta-blockade on the hypoglycemic response in insulin dependent diabetics. Lancet1979; 1: 458–62.
46.
HANSTENP.D.Beta-blocking agents and antidiabetic drugs. Drug Intell Clin Pharm1980; 14: 46–50.
47.
POPPD.A., TSET.F., SHAHS.D., CLUTTERW.E., CREYERP.E.Oral propranolol and metoprolol both impair glucose recovery from insulin-induced hypoglycemia in insulin-dependent diabetes mellitus. Diabetes Care1984; 7: 243–7.
48.
PODOLSKYS., PATTAVINAC.G.Hyperosmolar nonketotic diabetic coma: a complication of propranolol therapy. Metabolism1973; 22: 685–92.
49.
HOLTR.J., GASKINSJ.D.Hyperglycemia associated with propranolol and chlorpropamide coadministration. Drug Intell Clin Pharm1981; 15: 599–600.
50.
BROWNJ.D., STONED.B.Tolbutamide-induced hypoglycemia. Am J Clin Nutr1964; 15: 144–8.
51.
SOELDNERJ.S., STEINKEJ.Hypoglycemia in tolbutamide-treated diabetes. Report of two cases with measurement of serum insulin. JAMA1965; 193: 398–9.
52.
JOHNSONS.F., SCHADED.S., PEAKEG.T.Chlorpropamide-induced hypoglycemia. Successful treatment with diazoxide. Am J Med1977; 63: 799–804.
53.
LAMPEW.T.Hypoglycemia due to acetohexamide. Treatment by peritoneal dialysis. Arch Intern Med1967; 120: 239–41.
54.
JACKSONJ.E., BRESSLERR.Clinical pharmacology of sulfonylurea hypoglycemic agents. Part 2. Drugs1981; 22: 295–320.
55.
WALL-MANNINGH.J.Can beta blockers be used in diabetic patients?Drugs1979; 17: 157–60.
56.
GROOPL., TOTTERMANK.J.Propranolol does not inhibit sulfonylurea-stimulated insulin secretion in patients with noninsulin-dependent diabetes mellitus. Acta Endocrinol1982; 100: 410–5.
57.
POZZAG., MELOGIO., VIBERTIG.C.Studies on tolbutamide induced insulin secretion in man; effects of propranolol and theophylline (abstract). Diabetologia1972; S: 63.
58.
ROBERTSONR.P., HALTERJ.B., PORTED.A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus. J Clin Invest1976; 57: 791–5.
59.
DEDEVITIISO., GIORDANOF., GALLOB., JACONOA.Tolbutamide and propranolol (letter). Lancet1968; 1: 749.
60.
MASSARAF., STRUMIAE., CAMANNIE., MOLLNATTIG.M.Depressed tolbutamide-induced insulin response in subjects treated with propranolol. Diabetologia1971; 7: 287–9.
