Medical Research Society
4,
M II
THE ROLES OF INSULIN AND NORADRENALINE
IN HUMAN ESSENTIAL HYPERTENSION
therapy. This suggests that regular decreases in iCa. following foscamet
infusion, results in an attenuated PTH response. Whether this represents
funclinal hypoparathyroidismdue to e&auslion, decrease in the synthesis of
PTH or development of tolerance. following repeated activation of calcium
sensing receptors in the parathyrod cells, requires further claritation.
MW SAVAGE', V MOHAMED-ALlb,and G Williams"
'Diabetes and Endocrine Research Group, Department of
Medicine, The University of Liverpool, LIVERPOOL L69
3GA; and w i t t i n g t o n Hospital School of Medicine,
Archway Road, LONDON, N19 6UA
MI3
MS
PLAY
A
ROLE
IN
Department o f Medicine, University of Liverpool L69 3GA; 'Hannah
Research Institute, Ayr KA6 5HL,U.K.(*supporting member)
Lactation is characterized by enhanced appetite. Some, but not
all, studies show hypoinsulinaemia during lactation in the rat; this may
activate the neuropeptide Y system o f the hypothalamus and, hence,
hyperphagia.
Virtually all studies on serum hormone concentrations,
metabolic and other activities in lactating rats have involved sampling
in daylight hours when non-lactating (control) rats are in the postprandial period and food intake levels in lactating rats are lowest.
Therefore, we have investigated effects o f lactation on plasma insulin
and aspects o f adipose tissue metabolism 4 hours (h) into the dark
phase when rats are actively feeding and 4 h into the light phase when
feeding i s greatly reduced.
Nocturnal plasma insulin levels were 66% higher w0.05)
than
diurnal values in non-lactating rats, but n o such variable was observed
in lactating rats (pzO.05). Plasma insulin levels were 52% lower
(60.05) in lactating than control rats during the dark phase but were
not significantly different from non-lactating levels during the light
phase (pz0.05). Serum fatty acid concentrations changed in a
reciprocal manner with respect to serum insulin, decreasing by 50%
nocturnally in control rats (60.05).
Preliminary studies in which both groups o f rats were treated
for 3 days with 1 IU o f a slow release ('knte') insulin at 9.00 h and 2
or 5 IU of the same insulin at 17.00 h (control and lactating rats,
respectively) showed no effect of treatment on food intake in lactating
rats (p0.05) but suppressed nocturnal food intake by 95% @<0.001)
in control rats with a compensatory increase in diurnal food intake of
350-525% @<0.001) over the course of treatment.
These studies suggest that both hyperinsulinaemia and insulin
resistance may contribute to the hyperphagia of lacation.
FUNCTIONAL HYPOPARATHYROIDISM IN HIV SEROPOSITIVE
PATIENTS TREATED W H FOSCARNET FOR CMV RETINITIS.
TANG',
HYPOINSULINAEMIA
L PICKAVANCE, RG VERNON' and G WILLIAMS*
M 12
FH NOORMOHAMED. SY YEUNG'
8
BG GAZZARD'' and AF U N T ('introduced)
DOES
LACTATIONAL HYF'ERPHAGIA?
The question as to whether insulin resistance or
hyperinsulinaemia is a consequence, or a cause of
hypertension per se, remains controversial. We studied 6
hypertensive patients, blood pressure 161(9)1101(2) and 7
normotensive controls, blood pressure 122(6)176(4) mmHg,
(p<0.005) using two 3-hour oral glucose tolerance tests
(OGTT). In one of these tests the insulin response was
reduced with subcutaneous octreotide. After placebo,
hypertensives had slightly, but significantly, higher blood
glucose levels, (final results S.O(O.46) vs. 4.0(0.35) mmolll),
ANOVA, p<O.OOOl; but comparable insulin, ANOVA p>0.5.
Baseline noradrenaline (NA) levels were not different,
1.20(0.20)vs 1.65(0.05) nmolll respectively; however, levels
were consistently lower in the hypertensive group during the
OGlTs, ANOVA, p<O.OOl. NA levels rose from baseline in
response to glucose ingestion. Octreotide reduced the
insulin response and caused hyperglycaemia. Compared
with the placebo-OGTT, NA levels were lower in controls,
p<O.OOl, also in hypertensives, but not significantly,
p=0.056. Blood pressure did not change during any OGTT
in any subject. We conclude that physiological insulin levels
may raise NA levels, presumably by stimulating sympathetic
output to skeletal muscle. However, marked changes in
serum insulin were not associated with alterations in supine
blood pressure. This questions the hypothesis that insulin is
a prime-mover in the generation of essential hypertension.
YOULE".
Department of Clinical Pharmacology and Therapeutics, Imperial College
School of Medicine, and 'HIV Unit, Chelsea and Westminster Hosplal, 369
Fulham Road, LONDON, SWlO 9NH. UK.
Hypocalcaemia is a common finding in patients with Human
Immunodeficiency Wrus (HIV) infected patients. The concentrations of
bnised calcium (ica) in the e?3racellular fluid are held constant wilhin a very
narrow range of about 1.25 mmolil by the combined actions of parathyroid
hormone (PTH) and vitamin D. Changes in PTH responses may be a
possible cause in the genesis of hypocalcaemia in these patients. In the
present study we investigated the effect of acule changes in iCa. following
administration of foscarnet (phosphonoformate; 90 mgkg twice daily for 14
days) on plasma PTH levels in 7 HIV patients wlh CMV retinitis.
Baseline plasma iCa were (mmolfl; meaniSD) 1.24f0.05 (day 1; ~ 7 ) ;
1.32f0.08 (day7; P<0.05. 1117) and 1.39fo.12 (day 14; P<O.Ol. n=6) whist
the corresponding plasma intact PTH were (pglml): 2 2 f l l . 17f10 and 12flO
respectively (NS). Plasma iCa declined signifcantly to a similar value to
reach a nadir of 1.02 mmolll (range 0.91 to 1.22) on days 1 (n=3). 7 (n=7)
and 14 (17.6) of foscamet therapy. Plasma iCa recovered gradually and
returned to normal between 8 to 12h. By contrast plasma PTH rose
signifcantly (PcO.05) secondary to the decline in iCa. PTH peaked at (w/ml)
55 (range 30-64; day 1). 37 (range 18-74; day 7)and 33 (range 10-82: day
14) before declining as plasma iCa returned to baseline levels.
There was a signifcant inverse linear relationship between plasma C a and
circulating plasma PTH concentrations (r B 0.900, P<O.OOl) wilh the slope
(pglml PTH/mmol iCa) on day 1 (-110: 95% CI -164 to 59) being twice as
steep when compared to changes on day 14 (-50; 95% CI -63 to 33).
Decreases in plasma iCa concentrations were similar on all three occasions
but plasma PTH levels were generally lower on days 7 and 14 of fOSCamet
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MI4
THE HYPERPHAGIA IN HYPERINSULINAEMIC
HYPOGLYCAEMIC RATS IS INDEPENDENT OF LEPTlN
AND HYPOTHALAMIC NEUROPEPTIDE Y
.
Simon Dryden. Lucy Pickavance, Gareth Williams
Diabetes 8 Endocrinology Research Unit, Department of
Medicine, University of Liverpool. UK.
Neuropeptide Y (NPY) is a potent hypothalamic appetite
stimulant syntheised in the arcuate nucleus (ARC) and there
are NPY neurones projecting upwards to the PVN. the main
site of NPY release. Leptin. encoded by the obese (ob) gene
in white adipose tissue. reduces food intake and may act by
inhibiting NPY neurones. Insulin-induced hypoglycaemia
causes hyperphagia and weight gain, and we aimed to
determine whether NPY or leptin mediates this hyperphagia.
Male rats (n=8/group) were injected daily S.C. with insulin
(60 Ulkg) and either saline or leptin (150 pg). Untreated
control rats (n=8) were injected with saline, and all groups had
free access to food. Blood glucose was measured by tail-prick
daily, the insulin dose adjusted to maintain hypoglycaemia.
and food intake measured for 5 days.