the cardiovascular system ( Latouche et al. 2012 , Tarjus et al. 2015 ). Moreover, NGAL is a novel adipokine whose expression is increased in AT of obese subjects ( Catalan et al. 2009 ) and NGAL-knockout mice show improved insulin sensitivity
A Feraco, A Armani, R Urbanet, A Nguyen Dinh Cat, V Marzolla, F Jaisser, and M Caprio
Soo Bong Choi, Jin Sun Jang, Sang Mee Hong, Dong Wha Jun, and Sunmin Park
. Willi SM , Kennedy A, Wallace P, Ganaway E, Rogers NL & Garvey WT 2002 Troglitazone antagonizes metabolic effects of glucocorticoids in humans: effects on glucose tolerance, insulin sensitivity, suppression of free fatty acids, and leptin. Diabetes
A.-M. Mendes, R. J. Madon, and D. J. Flint
Cortisol implants in normal and diabetic rats reduced body weight, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in isolated adipocytes, whilst insulin sensitivity was unchanged. In normal but not diabetic rats these changes were accompanied by increased serum glucose and insulin concentrations.
In contrast, progesterone implants in normal and diabetic rats increased body weight gain, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in adipose tissue, again without affecting insulin sensitivity. Progesterone did not affect serum insulin concentrations in normal or diabetic rats but accelerated the decline in serum glucose concentrations which occurred during an overnight fast in diabetic rats.
The results suggest that (1) cortisol inhibits lipogenesis in adipose tissue without affecting insulin sensitivity, (2) cortisol reduces insulin binding in adipose tissue without a requirement for hyperinsulinaemia, which might itself indirectly lead to down-regulation of the insulin receptor, and (3) in diabetic rats progesterone stimulates lipogenesis in adipose tissue without any increase in food intake or serum insulin concentrations suggesting that progesterone may have a direct anabolic role in adipose tissue.
J. Endocr. (1985) 106, 225–231
CW Elton, JS Pennington, SA Lynch, FM Carver, and SN Pennington
Maternal diet during pregnancy has been reported to alter the offspring's ability to respond to a glucose challenge. The current studies report changes in basal and insulin-stimulated, in vitro glucose uptake in red (soleus) and white (extensor digitorum longus) muscle fiber types, as well as whole body insulin responsiveness of adult rat offspring associated with their mother's dietary fat and alcohol content during pregnancy. The offspring of Harlan-derived Sprague-Dawley female rats, dosed during pregnancy with ethanol (ETOH) via a liquid diet (35% of calories as ETOH) with either 12% or 35% of calories as fat, were compared with offspring from litters whose mothers were pair-fed an isocaloric amount of the liquid diet without ETOH. Maternal access to the liquid diets was terminated on day 20 of the pregnancies (sperm plug=day 0). The offspring were surrogate fostered within 48 h of birth to mothers which had consumed commercial chow throughout their pregnancy. Following weaning at 21 days of age, the offspring consumed only commercial rat chow and they were examined over the next 14 months for changes in glucose homeostasis as a consequence of in utero exposure to maternal dietary fat and/or alcohol. The 35% maternal fat diet resulted in both in vivo and in vitro decreases in insulin sensitivity. Thus, compared with adults whose mother's diet contained 12% fat, significant, in vitro muscle and in vivo whole body insulin resistance (measured by hyperinsulinemic-euglycemic clamping) was observed in adult rats whose mothers consumed 35% of dietary calories as fat. The addition of ethanol to the maternal 35% fat diet further reduced the offspring's red muscle tissues in vitro response to insulin, but did not affect whole body insulin sensitivity. Muscle basal and insulin-stimulated receptor tyrosine kinase activity were significantly decreased (approximately -50%) by the 35% fat maternal diet but there was no compensatory increase in serum insulin or glucose levels. Based upon both in vivo and in vitro data, these studies suggested that in utero exposure to 35% fat has a sustained effect on the adult offspring's glucose uptake/insulin sensitivity and that the effect is paralleled, at least in part, by decreased insulin receptor tyrosine kinase activity. In utero ETOH exposure resulted in the loss of basal and insulin-stimulated, in vitro glucose uptake in red muscle fibers but maternal dietary ETOH had no detectable effect on either in vivo insulin sensitivity or muscle tyrosine kinase activity.
AJ Forhead, JC Ousey, WR Allen, and AL Fowden
This study examined the effects of intrauterine growth on insulin secretion and resistance in newborn foals. Embryo transfer between small pony and large Thoroughbred mares was used to produce four groups of foals with different birth weights (pony in pony n=7; pony in Thoroughbred n=7; Thoroughbred in Thoroughbred n=8; Thoroughbred in pony n=8). On day 2 after birth, glucose (0.5 g/kg) was administered intravenously to the foal and blood samples were taken for 2 h to determine plasma glucose and insulin concentrations. On day 3, insulin sensitivity was assessed by giving insulin (0.75 U/kg i.v.) and measuring the decrement in plasma glucose in the foals. There were no significant differences in insulin secretion, insulin sensitivity or glucose tolerance between the control and growth-retarded Thoroughbred foals. Overgrown pony foals delivered by Thoroughbred mares had higher basal insulin levels and greater beta cell responses to glucose than the other groups of foals. The relationship between plasma glucose and insulin was also significantly steeper in overgrown pony foals than in the other groups. Variations in intrauterine growth rate, therefore, affect postnatal insulin secretion in the horse. More specifically, it is overgrowth, not growth retardation in utero that alters equine beta cell function in the immediate neonatal period.
I. M. D. JACKSON, K. D. BUCHANAN, M. T. McKIDDIE, and C. R. M. PRENTICE
An oral glucose tolerance test was performed in eight patients with gonadal dysgenesis and in two a diabetic response was found. The plasma insulin levels were estimated in response to the glucose load and were abnormal in five out of the six patients examined.
The blood sugar response to the standard insulin tolerance test was normal in six patients and showed increased insulin sensitivity in two. Plasma cortisol concentration was measured in response to the hypoglycaemia induced by insulin and in seven out of the eight patients rose considerably indicating a normally functioning pituitary-adrenal system.
The sera of all eight patients were examined for auto-antibodies and were essentially negative.
Possible reasons for the abnormalities in carbohydrate metabolism are discussed and it is suggested that gonadal dysgenesis may predispose to diabetes.
R. WILKINSON, R. HALL, A. COOPER, and D. J. NEWELL
Plasma non-esterified fatty acid (NEFA) levels during a standard insulin sensitivity test have been compared in hypopituitary and hospital control patients who had undergone full routine pituitary investigations. Significant impairment of the recovery of plasma NEFA levels after insulin injection was found in the hypopituitary group as a whole, but this finding was not consistent in individual cases. It is concluded that the measurement of NEFA levels is of little value in the diagnosis of mild hypopituitarism. Blood sugar levels after insulin were of no value in the diagnosis of minor degrees of hypopituitarism.
In 19 patients with mild hypopituitarism the order of frequency of deficiency of individual hormones, as judged by tests currently available, was gonadotrophins followed by growth hormone, adrenocorticotrophic hormone, thyroid-stimulating hormone, and antidiuretic hormone.
D Patiag, X Qu, S Gray, I Idris, M Wilkes, JP Seale, and R Donnelly
Angiotensin II (ANGII) increases insulin sensitivity in diabetic and non-diabetic subjects, even at subpressor doses, and because there is 'crosstalk' between ANGII and insulin-signaling pathways the underlying mechanism may not be due solely to changes in regional blood flow. A series of experimental studies was undertaken to evaluate the effects of ANGII on glucose and lipid metabolism in vivo and in vitro. Groups of fructose-fed, insulin-resistant Sprague-Dawley (SD) rats were pre-treated with 0.3 mg/kg per day of the AT(1)-receptor antagonist L-158 809 (n=16), or vehicle (n=16), by oral gavage. This was prior to an oral glucose tolerance test (day 5) and measurement of the effects of ANGII infusion (20 ng/kg per min i.v. for 3 h) on whole-body insulin sensitivity using the insulin suppression test (day 7). The effect of ANGII infusion on total triglyceride secretion rate (TGSR) was evaluated in normal SD rats pretreated for 7 days with L-158 809 (n=12) or vehicle (n=12). AT(1)- and AT(2)- receptor mRNA expression and [(3)H]2-deoxyglucose uptake were assessed in cultured L6 myoblasts. Short-term treatment with L-158 809 had no effect on glucose tolerance or fasting triglyceride levels in fructose-fed rats. ANGII infusion had no effect on insulin sensitivity in fructose-fed rats pretreated with vehicle (steady-state plasma glucose (SSPG) values 8.1+/-1.6 vs 8. 4+/-0.4 mmol/l), but pretreatment with L-158 809 resulted in ANGII having a modest insulin antagonist effect in this insulin-resistant model (SSPG values 9.6+/-0.3 vs 7.1+/-0.6, P<0.03). ANGII infusion had no significant effect on TGSR (e.g. 24.6+/-1.4 vs 28.4+/-0.9 mg/100 g per h in vehicle-treated animals). RT-PCR analysis showed that L6 cells express both AT(1)- and AT(2)-receptor mRNA. Incubation with ANGII (10(-9) and 10(-8) M) had no significant effect on the dose-response curve for insulin-stimulated [(3)H]2-deoxyglucose uptake. For example, C(I200) values (dose of insulin required to increase glucose uptake by 200%) were 4.5 x 10(-9) M (control) vs 3.9 x 10(-9) M and 6.2 x 10(-9) M, whereas the positive control (glucagon-like peptide-1) increased insulin sensitivity. Thus, ANGII infusion may have a modest insulin antagonist effect on glucose disposal in insulin-resistant fructose-fed rats pretreated with an AT(1)-blocker, but ANGII has no effect on TGSR or in vitro glucose uptake in L6 myoblasts. These findings are relevant to recent clinical discussions about the metabolic effects of ANGII and renin-angiotensin system blockade.
YL Wang-Fisher, J Han, and W Guo
Acipimox is a nicotinic acid-derived antilipolytic drug devoid of major side effects, and has been used in a number of human trials. This work reports the effects of Acipimox on leptin production from isolated rat adipocytes, in comparison with nicotinic acid and insulin. For cells isolated from normal animals, all these three reagents stimulated leptin release to a similar extent. Acipimox and nicotinic acid were more potent than insulin in stimulating leptin release from cells isolated from diabetic animals, probably because of impaired insulin sensitivity in cells from these diseased animals. Co-incubation of Acipimox with norepinephrine or dibutyryl cAMP diminished its stimulatory effects on leptin release, in parallel with increased lipolysis, suggesting that intracellular free fatty acids play an important role in mediating leptin production in adipocytes.
M. GRIFFITHS, D. L. McINTOSH, and R. M. C. LECKIE
Alloxan diabetes can be induced in red and in grey kangaroos and the initial changes in blood sugar levels after injection of the drug are similar to those in other herbivores, or in other vertebrates generally.
In general the presence or absence and the severity of catabolic effects of diabetes in rabbits, sheep and red kangaroos all eating the same diet depends on the amount of food eaten.
Injection of large amounts of cortisone into normal rabbits and a sheep induced the usual catabolic effects and injection of cortisone exacerbated the catabolism of diabetic rabbits and diabetic sheep. The same and larger dose rates of cortisone injected into 12 normal and two diabetic red kangaroos had no effect on N balance, hyperglycaemia, food intake, glycosuria, insulin sensitivity, or on intravenous glucose tolerance.