Further Studies on the Isolated Islets of Langerhans of Obese Hyperglycaemic Mice and their Normal Lean Littermates

Abstract

Investigation of mouse islet respiratory and secretory
activity has shown microdissected islets to be more suitable for
in Hits studies than collagenase isolated islets. The
hypersecretory activity of obese islets was verified and estimations
of LDH isoenzyme patterns have indicated substantial anaerobic
metabolism despite an increased capacity for oxygen uptake.

In vitro studies with normal and obese mouse islets or not
demonstrated a ºAMP or dbc-AMP stimulation of glucose induced
insulin secretion. A functional adenyl cyclase/ºAMP-phosphodiesterase
system has been demonstrated; operating at a higher level in obese
islets than in normal. The effects of pharmacological and
_insulinogenic agents on membrane bound cyclase activity was
investigated. Only limited correlation existed between the
stimulation of islet cyclase or inhibition of islet phosphodiesterase
and insulin secretion. The stimulation of islet adenyl cyclase was a
ß-adrenergic receptor function and its reduction an ∝-adrenergic
receptor function. Glucose does not initiate insulin secretion by the
direct stimulation of ß-cell adenyl cyclase. An alternative path
via glucagon has been suggested. The magnitude of cyclase and
phosphodiesterase activity was similar in normal and in obese islets.

The ionic requirements for insulin secretion were present in
normal and obese islet tissue.

Besides influencing directly the total biosynthesis and secretion
of newly synthesized insulin and proinsulin in normal and obese islets,
dbc-AMP may exert its effects on insulin secretion via islet glucose
metabolism. Dbc-AMP increased the activity of islet G6PDH and islet
glycogenolysis. Products of the latter may be utilised for the
resynthesis of ATP from ADP.

A correlation was made between the serum I.R.I. profile
and the morphological/biochemical constitution of obese islets
during the manifestation of the obese hyperglycaemic syndrome
with age.

The reis of the adenyl cyclase system in insulin
biosynthesis/secretion; islet glucose metabolism and the aetiology
of the obese hyperglycaemic syndrome in mice has been discussed.

Date of Award	1972
Original language	English