337 Short Communications
Horm. Metab. Res. 9 (1977) 337
© Georg Thieme Verlag Stuttgart Diurnal Variation of Pancreatic Alfa Cell Function F. Santeusanio l , M. Massi-BenedettrZ , G. Angeletti I
2
and P. Brunetti 2
Institute of Clinica Medica, and 21nstitute of Patologia Speciale Medica,University of Perugia. Italy
Diurnal variation of insulin secretion has been weU demonstrated in the recent years. Insulin response to oral (Jarrett and Keen 1969, Carrol and Nestei 1973) or intravenous glucose (Melllni, Verrillo, Marasco, Rivellese, Osorio and Bertolini 1976), tolbutarnide (Baker and Jarrett 1972), and glucagon (Meillni et al. 1976) appears less prompt and weaker in the afternoon. The purpose of our study is to verify if reduced insulin secretion in the afternoon is still present with a different stimulant of beta cell, arginine, and whether it is associated also with a diurnal variation of alpha ceU function.
Results Insulin response to arginine appeared significantly reduced at 10 and 20 minutes of the evening. infusional test. Similarly plasma glucagon levels were significantly lower during the first 20 minutes of the evening arginine test. No significant change was observed in the blood glucose curve (Table). Table. Different effect of arginine infusion on blood glucose (BG, mg/100 ml), plasma insulin (IRI, (IRG, pg/ml) in the morning ( .. ) and in the evening ( .... ). Min.
-15
BG"
68 ± 5 63 ± 1
65 ± 5 60 ± 1
IRI"
9±1 8±1 210 ± 32 212 ± 30
.... ....
IRG* **
(values are mean ± SEM). 0p
0
10
20
30
~U/ml)
and glucagon
60
74 ± 4 68 ± 1
80 ± 5 73 ± 1
78 ± 6 74 ± 1
57 ± 13 68 ± 3
9 ±1 8±1
31 ±4 22 ± 4+
47 ± 10 34 ± 10§
55 ± 13 43 ± 13
10 ± I l3± 2
210 ± 34 204 ± 30
465 ± 87 382 ± 66+
614 ± 105 517 ± 101'
666 ± 144 638 ± 142
305 ± 59 261 ± 37
< 0.01; +p < 0.025; § p < 0.05.
Discussion The data of our study seem to confirm the reduced ability of insulin secretion in the evening also in response to arginine stimulus; furthermore they show for the first time a diurnal variation of alpha ceU function. At present it is not possible to draw any conclusion about the physiological meaning of such a finding. However the intervention of a common factor able to depress both alpha and beta ceU function in the evening could be postulated. Somatostatin (SRIF) isolated from hypothalamus (Brazeau, Vale, Burgus, Ling and Butcher 1973) and more recently identified in D ceU of the islets of Langerhans (Orei, Beatens, Dubois and Rufener 1975) is the only substance known to have such an ability; although its physiological role in the humans is not yet clarified, a circadian variation of somatostatin hypothetically could be considered, influencing in a diurnal pattern also both alpha and the beta cell function. References
Baker, A./., R.J. Jarren' Lancet 2: 945 (1972). - Brazeau, P., W. Vale, R. Burgus, N. Ling. M. Butcher, J. Rivier, R. Guillemin: Science 179: 77 (1973). - Carroll, K.F., P. J. Nestei: Diabetes 22: 333 (973). - Jarrett, R.J., H. Keen: Brit.Med.J. 2: 341 (969). - Melllni, F., A. Verrillo, M Marasco, A. Rivellese, J. Osorio, MG. Berto/ini: Horm.Metab.Res. 8: 85 (1976). - Orei, L., D. Baetens, M.P. Dubois, C. Rufener: Horm.Metab.Res. 7: 400 (975). Requests for reprints should be addressed to: Dr. Fausto Santeusanio, Institute of Clinica Medica, University of Perugia, 1-06100 Perugia (Italy)
Rec.: 16 March 1977
Ace.: 23 May 1977
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Subjects and Methods Alpha and beta ceU function was investigated with arginine infusion test (0.5/kg b.w., over 30 min) in five healthy volunteers. In everyone the test was performed twice at 08.00 a.m. and at 06,00 p.m. with an interval of three days. The last meal, containing 700 calories with 70 mg of carbohydrates, was taken 10-12 hours before testing. Blood glucose was measured by glucose-oxidase method, plasma insulin (IRI) and plasma glucagon (lRG) by the radioimmunoassay glucagon antiserum 30K was employed. For statistical evaluation, the paired t-Test was used.
Horm. Metab. Res. 9 (1977) 337
© Georg Thieme Verlag Stuttgart Diurnal Variation of Pancreatic Alfa Cell Function F. Santeusanio l , M. Massi-BenedettrZ , G. Angeletti I
2
and P. Brunetti 2
Institute of Clinica Medica, and 21nstitute of Patologia Speciale Medica,University of Perugia. Italy
Diurnal variation of insulin secretion has been weU demonstrated in the recent years. Insulin response to oral (Jarrett and Keen 1969, Carrol and Nestei 1973) or intravenous glucose (Melllni, Verrillo, Marasco, Rivellese, Osorio and Bertolini 1976), tolbutarnide (Baker and Jarrett 1972), and glucagon (Meillni et al. 1976) appears less prompt and weaker in the afternoon. The purpose of our study is to verify if reduced insulin secretion in the afternoon is still present with a different stimulant of beta cell, arginine, and whether it is associated also with a diurnal variation of alpha ceU function.
Results Insulin response to arginine appeared significantly reduced at 10 and 20 minutes of the evening. infusional test. Similarly plasma glucagon levels were significantly lower during the first 20 minutes of the evening arginine test. No significant change was observed in the blood glucose curve (Table). Table. Different effect of arginine infusion on blood glucose (BG, mg/100 ml), plasma insulin (IRI, (IRG, pg/ml) in the morning ( .. ) and in the evening ( .... ). Min.
-15
BG"
68 ± 5 63 ± 1
65 ± 5 60 ± 1
IRI"
9±1 8±1 210 ± 32 212 ± 30
.... ....
IRG* **
(values are mean ± SEM). 0p
0
10
20
30
~U/ml)
and glucagon
60
74 ± 4 68 ± 1
80 ± 5 73 ± 1
78 ± 6 74 ± 1
57 ± 13 68 ± 3
9 ±1 8±1
31 ±4 22 ± 4+
47 ± 10 34 ± 10§
55 ± 13 43 ± 13
10 ± I l3± 2
210 ± 34 204 ± 30
465 ± 87 382 ± 66+
614 ± 105 517 ± 101'
666 ± 144 638 ± 142
305 ± 59 261 ± 37
< 0.01; +p < 0.025; § p < 0.05.
Discussion The data of our study seem to confirm the reduced ability of insulin secretion in the evening also in response to arginine stimulus; furthermore they show for the first time a diurnal variation of alpha ceU function. At present it is not possible to draw any conclusion about the physiological meaning of such a finding. However the intervention of a common factor able to depress both alpha and beta ceU function in the evening could be postulated. Somatostatin (SRIF) isolated from hypothalamus (Brazeau, Vale, Burgus, Ling and Butcher 1973) and more recently identified in D ceU of the islets of Langerhans (Orei, Beatens, Dubois and Rufener 1975) is the only substance known to have such an ability; although its physiological role in the humans is not yet clarified, a circadian variation of somatostatin hypothetically could be considered, influencing in a diurnal pattern also both alpha and the beta cell function. References
Baker, A./., R.J. Jarren' Lancet 2: 945 (1972). - Brazeau, P., W. Vale, R. Burgus, N. Ling. M. Butcher, J. Rivier, R. Guillemin: Science 179: 77 (1973). - Carroll, K.F., P. J. Nestei: Diabetes 22: 333 (973). - Jarrett, R.J., H. Keen: Brit.Med.J. 2: 341 (969). - Melllni, F., A. Verrillo, M Marasco, A. Rivellese, J. Osorio, MG. Berto/ini: Horm.Metab.Res. 8: 85 (1976). - Orei, L., D. Baetens, M.P. Dubois, C. Rufener: Horm.Metab.Res. 7: 400 (975). Requests for reprints should be addressed to: Dr. Fausto Santeusanio, Institute of Clinica Medica, University of Perugia, 1-06100 Perugia (Italy)
Rec.: 16 March 1977
Ace.: 23 May 1977
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Subjects and Methods Alpha and beta ceU function was investigated with arginine infusion test (0.5/kg b.w., over 30 min) in five healthy volunteers. In everyone the test was performed twice at 08.00 a.m. and at 06,00 p.m. with an interval of three days. The last meal, containing 700 calories with 70 mg of carbohydrates, was taken 10-12 hours before testing. Blood glucose was measured by glucose-oxidase method, plasma insulin (IRI) and plasma glucagon (lRG) by the radioimmunoassay glucagon antiserum 30K was employed. For statistical evaluation, the paired t-Test was used.
