Insulin and glucagon are glucoregulatory hormones that contribute to glucose homeostasis.
Plasma insulin is elevated during normoglycemia or hyperglycemia and acts as a
suppressor of glucagon secretion. We have investigated if and how insulin and glucose
contribute to the regulation of glucagon secretion through long term (48 h) elevated insulin
concentrations during simultaneous hypoglycemia or euglycemia in mid-lactating
dairy cows. Nineteen Holstein dairy cows were randomly assigned to 3 treatment
groups: an intravenous insulin infusion (HypoG, n ¼ 5) to decrease plasma glucose concentrations
(2.5 mmol/L), a hyperinsulinemic-euglycemic clamp to study effects of insulin
at simultaneously normal glucose concentrations (EuG, n ¼ 6) and a 0.9% saline infusion
(NaCl, n ¼ 8). Plasma glucose was measured at 5-min intervals, and insulin and glucose
infusion rates were adjusted accordingly. Area under the curve of hourly glucose, insulin,
and glucagon concentrations on day 2 of infusion was evaluated by analysis of variance
with treatments as fixed effect. Insulin infusion caused an increase of plasma insulin area
under the curve (AUC)/h in HypoG (41.9 8.1 mU/L) and EuG (57.8 7.8 mU/L) compared
with NaCl (13.9 1.1 mU/L; P < 0.01). Induced hyperinsulinemia caused a decline of
plasma glucose AUC/h to 2.3 0.1 mmol/L in HypoG (P < 0.01), whereas plasma glucose
AUC/h remained unchanged in EuG (3.8 0.2 mmol/L) and NaCl (4.1 0.1 mmol/L).
Plasma glucagon AUC/h was lower in EuG (84.0 6.3 pg/mL; P < 0.05) and elevated in
HypoG (129.0 7.0 pg/mL; P < 0.01) as compared with NaCl (106.1 5.4 pg/mL). The
results show that intravenous insulin infusion induces elevated glucagon concentrations
during hypoglycemia, although the same insulin infusion reduces glucagon concentrations
at simultaneously normal glucose concentrations. Thus, insulin does not generally have an
inhibitory effect on glucagon concentrations. If simultaneously glucose is low and insulin is
high, glucagon is upregulated to increase glucose availability. Therefore, insulin and
glucose are conjoint regulatory factors of glucagon concentrations in dairy cows, and the
plasma glucose status is the key factor to decide if its concentrations are increased or
decreased. This regulatory effect can be important for the maintenance of glucose homeostasis
if insulin secretion is upregulated by other factors than high glucose such as high
plasma lipid and protein concentrations at simultaneously low glucose.