Hyperthyroidism, Insulin and Metabolism
Rubenstein. A.H., J.L. Clark, F. Melani, D.F. Steiner: Secretion of proinsulin C-peptide by pancreatic betacell and its circulation in blood. Nature 244: 697 -699 (1969) Rubenstein, A.H.• M.B. Block, J. Sta", F. Melani. D.F. Steiner: Proinsulin and C-peptide in blood. Diabetes 21: Suppl. 2,661-672 (1972) Schatz, H., E.F. Pfeiffer: Release of immunoreactive and radioactively prelabelled endogenous (pro )insulin from isolated rat islets in the presence of exogenous insulin. J, Endocrinol. 74: 243-249 (1977) Thiel, M., U. Krause, G. Mangold. E. Wolf, J. Beyer: Untersuchungen zur Sekretion des Enteroglukagon bei Patienten nach totaler Duodenopankreatektomie. Verh. d. Deutschen Ges. f. innere Medizin 83: 1399-1402 (1977) Vance. J.E.• K.D. Bcchanan, R.H. Williams: Glucagon and insulin release. Influence of drugs affecting the autonomic nervous system. Diabetes 20: 78-82 (1971) Yanaihara. N., ,T. Hashimoto, C. Yanaihara, M. Sakagami, D. F. Stein er, A.H. Rubenstein: Synthesis of human connecting peptide derivatives and their immunological properties. Biochem. Biophys. Res. Commun. 59: 11241130 (1974)
Requests for reprints should be addressed to: Dr. Ulrich Krause, Abteilung f. Klin. Endokrinologie, Bau 5, Langenbeckstr.l, 0-6500 Mainz (Germany)
Horm. Metab. Res. 11 (1979) 265-270
Serum Insulin and Free Fatty Acid Responses to Siow and Quick Graded Hyperglycaemias in Hypothyroid Oogs* Aurora Renauld**, L.L. Andrade***, R.C. Sverdlik, R.R. Rodrfguez** and D.M. Lindental Institute of Physiology. Buenos Aires University Medical School, Buenos Aires, Argentina
Summary The effects of thyroidectomy by radioiodine on blood sugar, serum immunoreactive insulin and serum free faUy acid levels in dogs, in the course of glucose infusion tests whether involving glucose priming-dose (B tests) or not (A tests) were studied. The basal levels of blood sugar and serum insulin were not affected by hypothyroidism; circulating free fatty acids had -The present study was partly reported in abstract from (XI Congreso Latinoamericano de Ciencias Fisiologicas,
Mendoza, Argentina, July 29 - Agust 4, 1973; VIII Congreso Panamericano de EndocrinologIa, Buenos Aires, Argentina, October 27 - November 2, 1974). The study was sponsored by the "Consejo Nacional de Investigaciones CientIficas y Tecnicas", Argentina, Res. Grant no. 2304-d. "Established Investigator at this Council. -- Post-graduated Fellow, University of Buenos Aires, Argentina. Received: I Sept. 1976
Accepted: 2S Aug. 1978
oolB-5043/79
103.00
0432-0265
hardly risen. In the hypothyroid group, the blood sugar promes curing both tests were somewhat higher than normal, and hyperglycaemia was maintained for longer. These abnormalities were restored by Thyroxine therapy. Hypothyroidism brought about a considerable alteration of the dynamics of serum insulin response to glucose. Early during the continuous stimulation, serum insulin levels were normal (A tests) or somewhat higher than normal (B tests). Late during the stimulation or, even, after interruption of glucose infusion quite an intense insulin response was tardiIy observed, which was the major effect of hypothyroidism on the insulin response to continuous stimulation by glucose. The abnormalities of the serum insulin profile were corrected by thyroxine therapy. Foot Note: The following abbreviations will be used throughout the text: BS, blood sugar; IRI, immuno-reactive insulin; FFA, free fatty acids; BEI, butanol-extractable iodine; PBI, protein-bound iodine; T4, thyroxine.
© 1979 Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Krause, u., J. Beyer, U. Cordes, J. Happ: Serum-C-Peptidspiegel und Serllminsulin bei Patienten mit Hypoglykämien sowie unterschiedlichen Ober- und Unterfunktionszuständen des Inselsystems. IV. Internationales Donausymposium über Diabetes meUitus, Dubrovnik 1975 Krause, u., U. Cordes, J. Beyer: C-Peptid, Sekretion und Stoffwechsel bei unterschiedlichen Funktionszuständen und Störungen der B-Zellen der Langerhansschen Inseln. Dtsch. med. Wschr. 102: 785-790 (1977) Krause, u., H. Puchinger, A. Wacker: Inhibition of glucose induced insulin secretion in trypsin treated islets of Langerhans. Horm. Metab. Res. 5: 325-329 (1973) Kuzuya, T., A. Matsuda: Disappearance rate of endogenous human C-peptide from blood. Diabetologia 12: 519-521 (1976) Maier, v., E.F. Pfeiffer: Biosynthese und Sekretion von Insulin nach Behandlung von Langerhansschen Inseln mit Neuraminidase (abstract). Hoppe-Seyler's Z. physiol. Chem. 1546-1547 (1972) Pfeiffer. E.F.. S. Raptis: Controlled extension of oral antidiabetic therapy on former insulin dependent diabetics by means of the combined Lv. glibenclarnide-glucose response test. Diabetologia 8: 41-47 (1972)
265
Aurora Renauld, L.L. Andrade, R.C. Sverdlik, R.R. Rodriguez and D.M. Lindental
Hypothyroidism brought about a considerable alteration of the dynamics of serum insulin response to glucose. Early during the continuous stimulation, serum insulin levels were normal (A tests) or somewhat higher then normal (B tests). Late during the stimulation or, even, after interruption of glucose infusion quite an intense insulin response was tardiIy observed, which was the major effect of hypothyroidism on the insulin response to continuous stimulation by glucose. These abnormalities of the serum insulin proftle were corrected by thyroxine therapy. Serum free faUy acid levels of the thyroidectomized dogs fell during glucose infusion, whether significantly (A test) or not (B test), and no further rebound during the test period was observed. The basal values of serum free faUy acids of the thyroidectomized group hardly rose following thyroxine therapy; during the infusion, serum free faUy acids fell more intensely than in the untreated thyroidectomized dogs, but no further rebound despite the therapy was observed. Key-Words: Glucose Infusion Test - Blood Sugar - Serum Immunoreactive Insulin - Serum Free Fatty Acids - ·Hypothyroidism - Dogs
Introduction Glucose is a major stimulant of insulin secretion at a physiological level. Pancreatic stimulation by glucose as a ramp function evoked a gradually ascending insulin response in both normal, rats (Grodsky 1971) and dogs (Orsetti and Macabies 1968; Orsetti, Basseres and Macabies 1970). On the other hand, a diphasic pattern of insulin release over continuous pancreatic stimulation following glucose primingdose was observed both "in vitro" (Grotbky, Bennett, Smith and Nemencheck 1967; Grodsky and Bennett 1968; Grodsky, Curry, Landahl and Bennett 1969) and "in vivo" (Gerasi 1967; Renauld et al. 1974a). The present paper is concerned with the effect of hypothyroidism on the dynamies of the insulin response to continuous stimulation by glucose, whether preceded by glucose priming-dose or not. Preliminary studies on this response to glucose single pulmes demonstrated for it to be considerably promoted (Renauld, Sverdlik, Andrade and Rodriguez 1972; Renauld, Pinto, Sverdlik and Foglia 1973). Some metabolie effects of endogenous insulin, i.e. regulation of the BS and serum FF A levels, were also evaluated as weil as the corrective effect of T4 therapy on these parameters. Material and Methods Twenty male and two female, mongrel, adult dogs, wighing 12.2-23.3 kg, fed on dog chow pellets and water "ad libitum" were used. Thyroidectomy (two intraperitoneal injections of 1311Na, 1 mC/kg body wt, at 30 day-intervals) was performed by 4 years prior to experiments on 11 animals; the remainder of the dogs were kept as normal controls. Thyroxine therapy was aseries of 10 daily injections of sodium I-thyroxine (10 JIog/kg body wt/die, S.C., concentration 100 JIog/mJ); the last hormone dose was injected one ho ur prior to tests. On the day of experiments, after an ovcrnight fast the dogs were bled (peripheral vein); serum was separated for choles-
terol (kit, Wiener Argentina). The dogs were, then, anaestetized (sodium pentobarbital, 33 mg/kg body wt, i.v.) and tested ror glucose tolerance one hour later. Hyperglycaemia as a ramp function (A type tests) was achieved by continuous glucose infusion (dose: 16 mg/kg body wt, concentration 20 g/100 mJ) into a femoral vein at a constant rate (1.2 ml/min) by a Harvard Infusion Pump for one hour. During the B type tests, a quick glucose primingdose (700 rng/kg body wt, concentration 25 g/100 ml, femoral vein) was followed by a constant glucose infusion as in A Type experiments (glucose doses: 20 rng/kg body wt.). Blood sampies were taken (femoral vein) before, during and after the infusions, over 150 min-periods. Blood was assayed for a) BS, in a Technicon Autoanalyzer, modification of Microglucose N-80 1/11 technique
Rubenstein. A.H., J.L. Clark, F. Melani, D.F. Steiner: Secretion of proinsulin C-peptide by pancreatic betacell and its circulation in blood. Nature 244: 697 -699 (1969) Rubenstein, A.H.• M.B. Block, J. Sta", F. Melani. D.F. Steiner: Proinsulin and C-peptide in blood. Diabetes 21: Suppl. 2,661-672 (1972) Schatz, H., E.F. Pfeiffer: Release of immunoreactive and radioactively prelabelled endogenous (pro )insulin from isolated rat islets in the presence of exogenous insulin. J, Endocrinol. 74: 243-249 (1977) Thiel, M., U. Krause, G. Mangold. E. Wolf, J. Beyer: Untersuchungen zur Sekretion des Enteroglukagon bei Patienten nach totaler Duodenopankreatektomie. Verh. d. Deutschen Ges. f. innere Medizin 83: 1399-1402 (1977) Vance. J.E.• K.D. Bcchanan, R.H. Williams: Glucagon and insulin release. Influence of drugs affecting the autonomic nervous system. Diabetes 20: 78-82 (1971) Yanaihara. N., ,T. Hashimoto, C. Yanaihara, M. Sakagami, D. F. Stein er, A.H. Rubenstein: Synthesis of human connecting peptide derivatives and their immunological properties. Biochem. Biophys. Res. Commun. 59: 11241130 (1974)
Requests for reprints should be addressed to: Dr. Ulrich Krause, Abteilung f. Klin. Endokrinologie, Bau 5, Langenbeckstr.l, 0-6500 Mainz (Germany)
Horm. Metab. Res. 11 (1979) 265-270
Serum Insulin and Free Fatty Acid Responses to Siow and Quick Graded Hyperglycaemias in Hypothyroid Oogs* Aurora Renauld**, L.L. Andrade***, R.C. Sverdlik, R.R. Rodrfguez** and D.M. Lindental Institute of Physiology. Buenos Aires University Medical School, Buenos Aires, Argentina
Summary The effects of thyroidectomy by radioiodine on blood sugar, serum immunoreactive insulin and serum free faUy acid levels in dogs, in the course of glucose infusion tests whether involving glucose priming-dose (B tests) or not (A tests) were studied. The basal levels of blood sugar and serum insulin were not affected by hypothyroidism; circulating free fatty acids had -The present study was partly reported in abstract from (XI Congreso Latinoamericano de Ciencias Fisiologicas,
Mendoza, Argentina, July 29 - Agust 4, 1973; VIII Congreso Panamericano de EndocrinologIa, Buenos Aires, Argentina, October 27 - November 2, 1974). The study was sponsored by the "Consejo Nacional de Investigaciones CientIficas y Tecnicas", Argentina, Res. Grant no. 2304-d. "Established Investigator at this Council. -- Post-graduated Fellow, University of Buenos Aires, Argentina. Received: I Sept. 1976
Accepted: 2S Aug. 1978
oolB-5043/79
103.00
0432-0265
hardly risen. In the hypothyroid group, the blood sugar promes curing both tests were somewhat higher than normal, and hyperglycaemia was maintained for longer. These abnormalities were restored by Thyroxine therapy. Hypothyroidism brought about a considerable alteration of the dynamics of serum insulin response to glucose. Early during the continuous stimulation, serum insulin levels were normal (A tests) or somewhat higher than normal (B tests). Late during the stimulation or, even, after interruption of glucose infusion quite an intense insulin response was tardiIy observed, which was the major effect of hypothyroidism on the insulin response to continuous stimulation by glucose. The abnormalities of the serum insulin profile were corrected by thyroxine therapy. Foot Note: The following abbreviations will be used throughout the text: BS, blood sugar; IRI, immuno-reactive insulin; FFA, free fatty acids; BEI, butanol-extractable iodine; PBI, protein-bound iodine; T4, thyroxine.
© 1979 Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Krause, u., J. Beyer, U. Cordes, J. Happ: Serum-C-Peptidspiegel und Serllminsulin bei Patienten mit Hypoglykämien sowie unterschiedlichen Ober- und Unterfunktionszuständen des Inselsystems. IV. Internationales Donausymposium über Diabetes meUitus, Dubrovnik 1975 Krause, u., U. Cordes, J. Beyer: C-Peptid, Sekretion und Stoffwechsel bei unterschiedlichen Funktionszuständen und Störungen der B-Zellen der Langerhansschen Inseln. Dtsch. med. Wschr. 102: 785-790 (1977) Krause, u., H. Puchinger, A. Wacker: Inhibition of glucose induced insulin secretion in trypsin treated islets of Langerhans. Horm. Metab. Res. 5: 325-329 (1973) Kuzuya, T., A. Matsuda: Disappearance rate of endogenous human C-peptide from blood. Diabetologia 12: 519-521 (1976) Maier, v., E.F. Pfeiffer: Biosynthese und Sekretion von Insulin nach Behandlung von Langerhansschen Inseln mit Neuraminidase (abstract). Hoppe-Seyler's Z. physiol. Chem. 1546-1547 (1972) Pfeiffer. E.F.. S. Raptis: Controlled extension of oral antidiabetic therapy on former insulin dependent diabetics by means of the combined Lv. glibenclarnide-glucose response test. Diabetologia 8: 41-47 (1972)
265
Aurora Renauld, L.L. Andrade, R.C. Sverdlik, R.R. Rodriguez and D.M. Lindental
Hypothyroidism brought about a considerable alteration of the dynamics of serum insulin response to glucose. Early during the continuous stimulation, serum insulin levels were normal (A tests) or somewhat higher then normal (B tests). Late during the stimulation or, even, after interruption of glucose infusion quite an intense insulin response was tardiIy observed, which was the major effect of hypothyroidism on the insulin response to continuous stimulation by glucose. These abnormalities of the serum insulin proftle were corrected by thyroxine therapy. Serum free faUy acid levels of the thyroidectomized dogs fell during glucose infusion, whether significantly (A test) or not (B test), and no further rebound during the test period was observed. The basal values of serum free faUy acids of the thyroidectomized group hardly rose following thyroxine therapy; during the infusion, serum free faUy acids fell more intensely than in the untreated thyroidectomized dogs, but no further rebound despite the therapy was observed. Key-Words: Glucose Infusion Test - Blood Sugar - Serum Immunoreactive Insulin - Serum Free Fatty Acids - ·Hypothyroidism - Dogs
Introduction Glucose is a major stimulant of insulin secretion at a physiological level. Pancreatic stimulation by glucose as a ramp function evoked a gradually ascending insulin response in both normal, rats (Grodsky 1971) and dogs (Orsetti and Macabies 1968; Orsetti, Basseres and Macabies 1970). On the other hand, a diphasic pattern of insulin release over continuous pancreatic stimulation following glucose primingdose was observed both "in vitro" (Grotbky, Bennett, Smith and Nemencheck 1967; Grodsky and Bennett 1968; Grodsky, Curry, Landahl and Bennett 1969) and "in vivo" (Gerasi 1967; Renauld et al. 1974a). The present paper is concerned with the effect of hypothyroidism on the dynamies of the insulin response to continuous stimulation by glucose, whether preceded by glucose priming-dose or not. Preliminary studies on this response to glucose single pulmes demonstrated for it to be considerably promoted (Renauld, Sverdlik, Andrade and Rodriguez 1972; Renauld, Pinto, Sverdlik and Foglia 1973). Some metabolie effects of endogenous insulin, i.e. regulation of the BS and serum FF A levels, were also evaluated as weil as the corrective effect of T4 therapy on these parameters. Material and Methods Twenty male and two female, mongrel, adult dogs, wighing 12.2-23.3 kg, fed on dog chow pellets and water "ad libitum" were used. Thyroidectomy (two intraperitoneal injections of 1311Na, 1 mC/kg body wt, at 30 day-intervals) was performed by 4 years prior to experiments on 11 animals; the remainder of the dogs were kept as normal controls. Thyroxine therapy was aseries of 10 daily injections of sodium I-thyroxine (10 JIog/kg body wt/die, S.C., concentration 100 JIog/mJ); the last hormone dose was injected one ho ur prior to tests. On the day of experiments, after an ovcrnight fast the dogs were bled (peripheral vein); serum was separated for choles-
terol (kit, Wiener Argentina). The dogs were, then, anaestetized (sodium pentobarbital, 33 mg/kg body wt, i.v.) and tested ror glucose tolerance one hour later. Hyperglycaemia as a ramp function (A type tests) was achieved by continuous glucose infusion (dose: 16 mg/kg body wt, concentration 20 g/100 mJ) into a femoral vein at a constant rate (1.2 ml/min) by a Harvard Infusion Pump for one hour. During the B type tests, a quick glucose primingdose (700 rng/kg body wt, concentration 25 g/100 ml, femoral vein) was followed by a constant glucose infusion as in A Type experiments (glucose doses: 20 rng/kg body wt.). Blood sampies were taken (femoral vein) before, during and after the infusions, over 150 min-periods. Blood was assayed for a) BS, in a Technicon Autoanalyzer, modification of Microglucose N-80 1/11 technique
