Decreased Insulin- and Glucagon-Pulse Amplitude Accompanying β-Cell Deficiency Induced by Streptozocin in Baboons

The effect of β-cell deficiency on the spontaneous pulsatile secretory pattern of the islets of Langerhans was studied in the baboon. Measures of β-cell function were correlated with the secretory pattern before and at intervals after streptozocin administration. The degree of insulin deficiency was variable and ranged from mild to moderate. Highly regular pulses were less prevalent in baboons compared with rhesus monkeys and humans, but the mean frequency was similar and was not affected by treatment. The principal effect of β-cell destruction was to proportionately reduce the pulse amplitude of insulin (−39%, P < .003) without detectable change in pulse frequency, interhormonal phase relationship, or the regularity of pulses. Glucagon-pulse amplitude also fell (−19%, P < .09), but not significantly. However, glucagon-pulse amplitude was strongly correlated with insulin-pulse amplitude (r = −.59, P < .002), whereas mean fasting plasma concentrations of insulin and glucagon were not significantly changed after treatment. Because streptozocin affects only the β-cell, the data indicate a major influence of the insulin pulse on the α-cell secretory pulse. The data do not support the presence of a separate pacemaker for the α-cell but do not eliminate this possibility. The strong correlation of reduction in insulin-pulse amplitude with increasing fasting glucose and decreasing glucose disappearance lends support to growing evidence that the pattern of insulin secretion is an important determinant of normal glucose homeostasis.