Lethal Escherichia coli septicemia in the baboon: Alpha-adrenergic inhibition of insulin secretion and its relationship to the duration of survival

Philip E. Cryer, Arnold G. Coran, Jonas Sode, Clifford M. Herman, David L. Horwitz

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

To clarify the mechanisms of septicemic hypoinsulinemia and septicemic hyperglycemia, the serum immunoreactive insulin and serum glucose responses to Escherichia coli septicemia produced during phentolamine-induced α-adrenergic receptor blockade were measured in 7 baboons. Septicemic animals not given phentolamine were significantly hypoinsulinemic and hyperglycemic 15 minutes after E. coli injection. In contrast, during septicemia in α-adrenergic receptor blockaded baboons the mean serum immunoreactive insulin and glucose levels were not significantly different from those of control animals given saline rather than E. coli. Thus, α-adrenergic receptor blockade prevented both septicemic hypoinsulinemia and septicemic hyperglycemia. Furthermore, in 2 of 3 additional baboons given a single injection of phentolamine 20 minutes after E. coli injection, the depressed immunoreactive insulin levels increased and the elevated glucose values fell following phentolamine injection. Thus, the release of endogenous insulin (like the injection of exogenous insulin in earlier studies) aborted the developing hyperglycemia of septicemia indicating that septicemic hyperglycemia is not an obligatory response to factors other than insulin lack. Following smaller doses of E. coli, and with fluid infusion during septicemia, only 3 of 6 baboons developed definite hypoinsulinemia. The duration of survival of these 6 animals was significantly correlated with the serum immunoreactive insulin levels, expressed as a per cent of the mean of 2 base line observations for each animal, determined at 30, 45, and 60 minutes after E. coli injection. The mean duration of survival of the 3 hypoinsulinemic animals was significantly shorter than that of the 3 euinsulinemic animals The infusion of glucose, regular insulin, and potassium chloride did not prolong the duration of survival of 5 septicemic baboons beyond that seen in 6 septicemic animals not infused with these materials. However, the mean duration of survival of the 4 glucose-insulin-potassium-infused septicemic baboons which were initially hypoinsulinemic was significantly longer than that of the 3 hypoinsulinemic septicemic animals infused with fluids not containing glucose, insulin, and potassium chloride.

Original languageEnglish
Pages (from-to)622-638
Number of pages17
JournalThe Journal of Laboratory and Clinical Medicine
Volume79
Issue number4
StatePublished - Apr 1972

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