Effects of insulin and IGF1 on SMCs

More than a decade ago different publications showed that insulin stimulates SMC proliferation in vitro (Stout 1990). We have observed that in non-cultured cells, SMCs directly taken from the human artery, insulin stimulates collagen secretion. This effect was probably produced by activation of the IGF1 receptors, because addition of insulin receptor-blocking antibodies did not show any inhibition. On the contrary, antibodies blocking IGF1 receptors inhibited the insulin-induced collagen...

Endocrinology of ageing

In men, several hormonal systems show a gradual decline in activity during ageing, represented by a decrease in their bioactive hormone concentrations. The 'andropause' is characterized by a gradual decline in serum total and bioavailable testosterone, due to a decrease in testicular Leydig cell numbers and in their secretory capacity, as well as by an age-related decrease in episodic and stimulated gonadotropin secretion (Vermeulen 1991). Both cross-sectional (Vermeulen 1991) and longitudinal...

Ageing and lifespan in GHIGF1deficient mice

Several mouse models with GH IGF1 deficiency are available to study the influence of these hormones on ageing and longevity (lifespan). Due to the IGF1 deficiency all homozygous affected mice are dwarfed and they divide as the human models into MPHD including GH (e.g. the Ames dwarf mice and the Snell dwarf mice) and primary IGF1 deficiency (the Laron mouse). These mice first described by Schaible & Gowen (1961) have a mutation in a transcription factor for all anterior pituitary hormones...

The incretin effect in ageing and in type 2 diabetes

Incretin is the umbrella term to cover the multiple gut factors (now known to be hormones) which augment insulin response above that which can be attributed to glucose alone. This insulinotropic effect has been demonstrated by matching the time course of the plasma glucose excursion following an OGTT with both an i.v. infusion of glucose (Perley & Kipnis 1967) and during a hyperglycaemic clamp. In the hyperglycaemic clamp, plasma glucose was increased to * 11 mmol l for 2 h on two different...

Fertility

Paternity is well established at the oldest age so the natural history of male fertility is concluded only by death. By contrast, female fertility, terminating naturally at menopause, occupies only half of average adult life expectancy. Despite the enduring fertility potential, fathers older than 50 years are responsible for only *1 of births in developed countries. Communal procreative patterns are determined by the similarity of couple's age and the overwhelming age-restriction of female...

Ageing and the HPA axis

The background provided above is necessary for understanding the potential influence of ageing on the HPA axis and its associated tight network of other neuroendocrine reactions. One may ask whether this system is ageing by what might be called a 'normal' age-related process or if the wear and tear of today's complex, hectic living conditions are involved. As will be seen, it is difficult to separate these two factors. In order to separate out the effects of a 'normal' ageing process from the...

The impact of the HPA axis on human health

Since it is almost impossible to separate the effects of ageing and cumulative stress on the regulation of the HPA axis, it might be of interest to examine how the HPA axis activity is associated with diseases that are characteristic of ageing. This assumes that the insults on the HPA axis of wear and tear are an unavoidable consequence of ageing. Longevity runs in families and 'successful' ageing is likely to have genetic components. Perturbations of the regulation of the HPA axis and...

Ageing stress and the brain

Pacific Behavioral Research Foundation, 26386 Carmel Rancho Lane, Suite 202, PO Box 223040, Carmel, CA 93922-3040, USA Abstract. Ageing of the brain is an important factor in overall ageing and mortality, and new insights have clarified the relationship between neuroregulation and ageing. First, neuronal loss in normal ageing is now known to be a minor change. Loss of synapses through dystrophic neuronal change is the hallmark of normal ageing. Second, similar dystrophic changes occur in the...

The effect of insulin and IGF1 on the cytoskeleton in relation to SMC migration

The cytoskeleton is a complex network of protein filaments extending throughout the cytoplasm that is involved in a range of cell processes. Of the three main 10 min after insulin 10 imin after insulin + diltiazem FIG. 2. Insulin-induced F-actin reorganization near the membrane of human vascular smooth muscle cells showing a ruffling which does not appear when Ca2+ channels of these cells are blocked by diltiazem. The results are similar in the case of IGF1 (unpublished). 10 min after insulin...

Growth hormone axis

In the acute phase circulating levels of growth hormone (GH) are elevated. The peak GH levels as well as interpulse concentrations are high (Ross et al 1991, Voerman et al 1992) and the GH pulse frequency is increased. Serum insulin-like growth factor (IGF)1 concentrations are low, (Ross et al 1991). The combination of high GH levels and low IGF1 levels has been interpreted as resistance to GH, which may be related to decreased GH receptor expression (Hermansson et al 1997). The other...

Animal studies

An approach to this problem might be to study the regulation of the HPA axis in the ageing laboratory rat. Such animals are probably less exposed to varying external stressors than humans are. Furthermore, the primitive mechanisms involved are probably common to most mammals because they are essential for survival, and the results from rats should therefore be reasonably applicable to humans. The results of such studies indicate that the ageing rat has an increased corticosterone secretion...

IGF1 and insulin secretion during ageing

The secretion of GH decreases with advancing age, mainly through a decrease in the amplitude of GH pulses (Veldhuis et al 1995). Mean 24 h GH concentrations decline from late puberty into old age (Rudman et al 1981) due to decreased GH production and an increased clearance rate (Iranmanesh et al 1991). The changes in IGF1 levels throughout life appear to mimic those of GH (Ho et al 1987). Accordingly, in a cross-sectional study of healthy adults with similar lean body mass (LBM), the IGF1 blood...

Ageing of the normal brain

Until recently, ageing and senility were considered firm partners. We now know, however, that normal ageing ofthe brain is a process distinct from the degenerative dementias. Early neuropathology studies led to the dogma that up to 40 of neurons inexorably died over the lifespan. That belief was overturned by improved methodology using unbiased stereological techniques (Morrison & Hof 1997). In ageing primates and ageing rodents, rather than a loss of cortical pyramidal cells there is...

Atherogenity of insulin

Clinical studies have demonstrated that those processes linked to hyperinsulinaemia, such as type 2 diabetes or obesity, show a higher mortality due to coronary or cerebral atherosclerosis (Pyorala et al 1985). Furthermore, experimental results show that insulin acts on the vascular wall, either producing hypertension and endothelial changes, or influencing the smooth muscle cells (SMCs) to proliferate. It is well known that endothelial lesions and SMC proliferation are basic steps of...

Glucose tolerance glucose utilization and insulin secretion in ageing

Muller*, Josephine M. Egan*, Reubin Andres*, Johannes Veldhuisf and Graydon S. Meneilly Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, *Eaboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore 21224, MD, University of Virginia, Division of Endocrinology and Metabolism, Charlottesville, VA 22908, USA, and Department of Medicine, University of...

The hypothalamopituitaryovarian axis

The hypothalamo pituitary ovarian axis is a classical example of a closed loop endocrine negative feedback system. Pulsatile secretion of gonadotropin-releasing hormone (GnRH), from hypothalamic peptidergic neurons drives the pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. Whilst LH secretion depends on GnRH input, there is a GnRH-independent component of FSH secretion, probably driven by intrapituitary secretion of activin...

The thyroid axis in ageing

Holger Leitolf, Jens Behrends and Georg Brabant1 Department of Clinical Endocrinology, Center for Internal Medicine and Dermatology, Medizinische Hochschule Hannover (MHH), 30625 Hannover, Germany Abstract. The hypothalmo pituitary thyroid axis, among various endocrine systems, undergoes physiological alterations associated with the ageing process. Directly age-related changes have to be distinguished from indirect modifications which are caused by simultaneous thyroidal or non-thyroidal...

Beldyes Sex

Abbasi AA, Drinka PJ, Mattson DE, Rudman D 1993 Low circulating levels of insulin-like growth factors and testosterone in chronically institutionalized elderly men. J Am Geriatr Soc 41 975-982 Abbasi A, Duthie EH Jr, Sheldahl L et al 1998 Association of dehydroepiandrosterone sulfate, body composition, and physical fitness in independent community-dwelling older men and women. J Am Geriatr Soc 46 263-273 Aleman A, Verhaar HJ, De Haan EH et al 1999 Insulin-like growth factor-I and cognitive...

Ovulation disturbances and perimenopause

The following will briefly describe the perimenopausal prevalence and incidence of ovulation disturbances while expanding on a previous review (Prior 1998). Cross-sectional data will be reviewed before the prospective and epidemiological data are examined. The earliest cross-sectional studies of ovulation in 40 50 year old women used non-quantitative basal temperature methods. Collett et al (1954) documented 302 cycles from 146 women aged 17 50 using the basal temperature nadir (assessed...

Ageing and water homeostasis

David Robertson, Jens Jordan , Giris Jacobf, Terry Ketch, John R. Shannon and Italo Biaggioni Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology Vanderbilt University, Nashville TN 37232-2195, USA, Clinical Research Center, Franz Volhard Institut, Berlin, Germany and Recanati Autonomic Dysfunction Center, Rambam Medical Center, Haifa, Israel Abstract. This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology...