Stimulation of adipose tissue lipolysis following insulin-induced hypoglycaemia: evidence of increased beta-adrenoceptor-mediated lipolytic response in IDDM.

Abstract:

:The adrenergic regulation of adipose tissue lipolysis in response to insulin-induced hypoglycaemia (intravenous infusion of soluble insulin 0.10 IU.kg body weight-1.h-1 until the arterial plasma glucose fell below 2.8 mmol/l) was investigated directly in vivo in 11 insulin-dependent diabetic (IDDM) patients and 12 control subjects, using microdialysis of the extracellular space of abdominal subcutaneous adipose tissue. The tissue glycerol level (lipolysis index) and the escape of ethanol from the perfusion medium (blood flow index) were continuously monitored. During insulin infusion the arterial glucose level was reduced in parallel and the hypoglycaemic nadir was almost identical in the two groups (diabetic patients 2.2 +/- 0.1 and control subjects 2.3 +/- 0.1 mmol/l). While the maximum response of plasma epinephrine to hypoglycaemia was 30% lower in diabetic patients than in the control subjects (p < 0.05), the glycerol levels in adipose tissue and in plasma, as well as in serum non-esterified fatty acids, increased twice as much in the former as in the latter group following hypoglycaemia (p < 0.01). Addition of the beta-adrenoceptor blocker propranolol (10(4) mol/l) to the tissue perfusate almost completely prevented the hypoglycaemia-induced increase in the adipose tissue glycerol level in both groups, whereas in situ perfusion with 10(-4) mol/l of the alpha-adrenoceptor blocker phentolamine resulted in an additional increase in the tissue glycerol levels; during alpha-blockade, the glycerol response to hypoglycaemia remained enhanced by threefold in the diabetic patients (p < 0.01). In both groups local adipose tissue blood flow increased transiently in a similar way after hypoglycaemia; the increase being inhibited by in situ beta-adrenoceptor blockade. We conclude that both alpha- and beta-adrenergic mechanisms regulate adipose tissue lipolysis in response to hypoglycaemia. In IDDM, lipolysis is markedly enhanced following hypoglycaemia, despite a reduced catecholamine secretory response, because of increased beta-adrenoceptor action in adipose tissue.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Bolinder J,Sjöberg S,Arner P

doi

10.1007/s001250050519

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

845-53

issue

7

eissn

0012-186X

issn

1432-0428

journal_volume

39

pub_type

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