Abstract
Glucagon response to insulin-induced hypoglycaemia is impaired in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg-1 min-1 for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 μg kg-1) in chloral hydrate-anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg-1 subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L-1. As expected, the plasma glucagon response was reduced by ~ 45% in streptozotocin-diabetic rats compared with controls (P = 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 ± 92 pg mL-1 in controls (P=0.009) and by 570 ± 137 pg mL-1 in the diabetic rats (P = 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P = 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 ± 208 pg mL-1 (P < 0.001) in controls but only by 555 ± 242 pg mL-1 in the diabetic rats (P = 0.049). Thus, the plasma glucagon response to carbachol was impaired by ~ 58% in the diabetic rats (P = 0.028). We conclude that carbachol-stimulated glucagon secretion is impaired concomitantly with the impaired glucagon response to hypoglycaemia in streptozotocin-diabetic rats, whereas adrenaline-induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulin-induced hypoglycaemia in diabetes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 215-221 |
| Number of pages | 7 |
| Journal | Acta Physiologica Scandinavica |
| Volume | 155 |
| Issue number | 2 |
| State | Published - 1995 |
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Keywords
- Adrenaline
- Cholinergic
- Diabetes
- Glucagon secretion
- Hypoglycaemia
- Rats
ASJC Scopus subject areas
- Physiology
Cite this
Glucagon secretory response to hypoglycaemia, adrenaline and carbachol in streptozotocin-diabetic rats. / Ahren, B.; Stern, J. S.; Gingerich, R. L.; Curry, D. L.; Havel, Peter J.
In: Acta Physiologica Scandinavica, Vol. 155, No. 2, 1995, p. 215-221.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucagon secretory response to hypoglycaemia, adrenaline and carbachol in streptozotocin-diabetic rats
AU - Ahren, B.
AU - Stern, J. S.
AU - Gingerich, R. L.
AU - Curry, D. L.
AU - Havel, Peter J
PY - 1995
Y1 - 1995
N2 - Glucagon response to insulin-induced hypoglycaemia is impaired in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg-1 min-1 for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 μg kg-1) in chloral hydrate-anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg-1 subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L-1. As expected, the plasma glucagon response was reduced by ~ 45% in streptozotocin-diabetic rats compared with controls (P = 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 ± 92 pg mL-1 in controls (P=0.009) and by 570 ± 137 pg mL-1 in the diabetic rats (P = 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P = 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 ± 208 pg mL-1 (P < 0.001) in controls but only by 555 ± 242 pg mL-1 in the diabetic rats (P = 0.049). Thus, the plasma glucagon response to carbachol was impaired by ~ 58% in the diabetic rats (P = 0.028). We conclude that carbachol-stimulated glucagon secretion is impaired concomitantly with the impaired glucagon response to hypoglycaemia in streptozotocin-diabetic rats, whereas adrenaline-induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulin-induced hypoglycaemia in diabetes.
AB - Glucagon response to insulin-induced hypoglycaemia is impaired in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg-1 min-1 for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 μg kg-1) in chloral hydrate-anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg-1 subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L-1. As expected, the plasma glucagon response was reduced by ~ 45% in streptozotocin-diabetic rats compared with controls (P = 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 ± 92 pg mL-1 in controls (P=0.009) and by 570 ± 137 pg mL-1 in the diabetic rats (P = 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P = 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 ± 208 pg mL-1 (P < 0.001) in controls but only by 555 ± 242 pg mL-1 in the diabetic rats (P = 0.049). Thus, the plasma glucagon response to carbachol was impaired by ~ 58% in the diabetic rats (P = 0.028). We conclude that carbachol-stimulated glucagon secretion is impaired concomitantly with the impaired glucagon response to hypoglycaemia in streptozotocin-diabetic rats, whereas adrenaline-induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulin-induced hypoglycaemia in diabetes.
KW - Adrenaline
KW - Cholinergic
KW - Diabetes
KW - Glucagon secretion
KW - Hypoglycaemia
KW - Rats
UR - http://www.scopus.com/inward/record.url?scp=0028807543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028807543&partnerID=8YFLogxK
M3 - Article
C2 - 8669294
AN - SCOPUS:0028807543
VL - 155
SP - 215
EP - 221
JO - Acta Physiologica Scandinavica
JF - Acta Physiologica Scandinavica
SN - 0370-839X
IS - 2
ER -