The renal response to exogenous insulin in non-insulin-dependent diabetes mellitus in relation to blood pressure and cardiovascular hormonal status.
BACKGROUND
Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance hyperinsulinaemia and a high frequency of hypertension. It has recently been shown that insulin exerts a sodium-retaining effect, which is preserved in NIDDM: We sought to determine whether insulin affected renal sodium handling differently in hypertensive and normotensive NIDDM patients.


METHODS
After a baseline period of 2 h, eight normotensive (N-) NIDDM patients and eight NIDDM patients with hypertension (H-) underwent a euglycaemic clamp with infusion of two sequential doses of insulin (50 and 500 mU/kg/h) or vehicle (time control) during 2-h periods each. Fractional clearances of sodium and lithium were determined according to standard methods. Fractional lithium clearance was used to assess segmental tubular sodium handling.


RESULTS
Insulin induced similar decrements in fractional sodium excretion (N-NIDDM: 43+/-5.9 and 57+/-9.1%,H-N IDDM: 48+/-16.4 and 62+/-12.5%, low and high insulin dose respectively). Distal tubular sodium absorption increased simultaneously. A fall in fractional proximal sodium reabsorption was observed in N-NIDDM (4.4+/-2.7 and 29.8+/-5.1%, low and high insulin dose respectively), which was attenuated in H-NIDDM (-5.0+/-7.3 and -2.1+/-13.9% respectively). The latter appeared to be related to a defective atrial natriuretic factor (ANF) and renal cyclic GMP response. A modest decrease in blood pressure occurred during insulin infusion that was not related to changes in ANF or FeLi.


CONCLUSIONS
The findings suggest that insulin-induced sodium retention may contribute to hypertension in NIDDM if the homeostatic response to offset this effect fails.
Gans
R O
RO
Department of Medicine, ICaR-VU Research School Cardiovascular Diseases, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Bilo
H J
HJ
Donker
A J
AJ
D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000502:physiology*; D002319:Cardiovascular System / Q000503:physiopathology; D016022:Case-Control Studies; D006152:Cyclic GMP / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000209:etiology / Q000503:physiopathology; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D012083:Renin / Q000097:blood
D007328:Insulin; D009320:Atrial Natriuretic Factor; D012083:Renin; D006152:Cyclic GMP