Clinical Neuroscience

[BRAIN INSULIN SIGNALLING IN THE REGULATION OF ENERGY BALANCE AND PERIPHERAL METABOLISM]

MICHAELA Diamant

MARCH 20, 2007

Clinical Neuroscience - 2007;60(03-04)

[The unparalleled global rates of obesity and type 2 diabetes, together with the associated cardiovascular morbidity and mortality, are referred to as the "diabesity pandemic". Changes in lifestyle occurring worldwide, including the increased consumption of high-caloric foods and reduced exercise, are regarded as the main causal factors. Central obesity and insulin resistance have emerged as important linking components. Understanding the aetiology of the cluster of pathologies that leads to the increased risk is instrumental in the development of preventive and therapeutic strategies. Historically, skeletal muscle, adipose tissue and liver were regarded as key insulin target organs involved in insulinmediated regulation of peripheral carbohydrate, lipid and protein metabolism. The consequences of impaired insulin action in these organs were deemed to explain the functional and structural abnormalities associated with insulin resistance. The discovery of insulin receptors in the central nervous system, the detection of insulin in the cerebrospinal fluid after peripheral insulin administration and the well-documented effects of intracerebroventricularly injected insulin on energy homeostasis, have identified the brain as an important target for insulin action. In addition to its critical role as a peripheral signal integrating the complex network of hypothalamic neuropeptides and neurotransmitters that influence parameters of energy balance, central nervous insulin signalling is also implicated in the regulation of peripheral glucose metabolism. This review summarizes the evidence of insulin action in the brain as part of the multifaceted circuit involved in the central regulation of energy and glucose homeostasis, and discuss the role of impaired central nervous insulin signalling as a pathogenic factor in the obesity and type 2 diabetes epidemic.]

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

[THE GHRELIN SYSTEM: PHYSIOPATHOLOGICAL INVOLVEMENT IN THE CONTROL OF BODY GROWTH AND ENERGY METABOLISM]

JACQUES Epelbaum

[This short review will summarize some recent findings on the physiopathology of the endogenous ghrelin/obestatin system by focussing on experimental studies aiming at blocking the effects of endogenous ghrelin and clinical studies investigating genotype/phenotype correlations concerning the genes encoding for ghrelin and its cognate receptor.]

Clinical Neuroscience

[OPTIMAL ALIGNMENT®. NOVEL SOFTWARE PROCEDURE FOR 3D RECONSTRUCTION OF ELECTRONMICROSCOPIC SERIAL SECTIONS]

SIMON László, GARAB Sándor, NOSZEK Annamária, ELIZABETH Römmer, ZÁBORSZKY László

[3D reconstruction from electronmicroscopic (EM) serial sections substantially differs from modeling body parts by linking convoluted planes delivered by CT and NMR. Namely, variations both in relative X-Y position and rotation of the target elements between the adjacent images and also additional problems caused by deformed, deteriorated or missing sections can only be overruled by an aligning paradigm, which exploits all the pixel-level information, and results in an optimal fitting with selected precision. This paper presents a complex computer program called Optimal Alignment®, which performs the precise elaboration of X-Y shift and relative rotation of two consecutive images. The required searching process will be customized by setting four independent parameters which relate the span and density of the pixel-scanning basic process. Optimalization of fitting accuracy versus running time can be achieved by a rather short training period. The potential precision of Optimal Alignment based on complex algorythms is far superior to manual aligning of EM photographs with the eye-wrist-mouse facility. The resulted database of alignment orientation parameters can serve as an advanced source for the 3D reconstructing programs. Optimal Alignment® software tool (supported by Hungarian Space Office grant TP 138) will be demonstrated on a basal forebrain NPY+ axonal reconstruction, performed in L. Záborszky’s laboratory (supported by NIH grant NSO23945).]

Clinical Neuroscience

[PROTECTIVE ACTION OF SNAKE VENOM NAJA NAJA OXIANA AT SPINAL CORD HEMISECTION]

ABRAHAMYAN S. Silva, MELIKSETYAN B. Irina, CHAVUSHYAN A. Vergine, ALOYAN L. Mery, SARKISSIAN S. John

[Based on data accumulated regarding the neuroprotective action of Proline-Rich-Peptide-1 (PRP-1, a fragment of neurophysin vasopressin associated hypothalamic glycoprotein consisting of 15 amino acid residues) on neurons survival and axons regeneration and taking into the account that LVV-Hemorphin-7 (LVV-H7, an opioid peptide, widely distributed in different cell types of various tissues of intact rats, including those of the nervous and immune systems) derived from the proteolitic processing of hemoglobin in response to adverse environmental and physiological conditions, possesses the anti-stressor properties, we used histochemistry, immunohistochemistry and electrophysiology to investigate the putative neuroprotective action of Central Asian Cobra Naja naja oxiana snake venom (NOX) on trauma-injured rats. ABC immunohistochemical method and histochemical method on detection of Ca2+- dependent acid phosphatase activity were used for the morpho-functional study. By recording the electrical activity of the signals from the single neurons in and below the SC injury place, NOX venom has been shown to result in the complete restoration of hypothalamic-spinal projections originated from ipsi- and contra-lateral PVN and SON to neurons of SC lumbar part. NOX prevented the scar formation, well observed two months after SC injury in the control rats, resulted in the regeneration of nerve fibers growing through the trauma region, survival of the PRP-1- and LVV-H7-immunoreactive (Ir) neurons, and increase of the PRP-1- and LVV-H7-Ir nerve fibers and astrocytes in the SC lesion region. NOX was suggested to exert the neuroprotective effect, involving the PRP-1 and LVV-H7 in the underlying mechanism of neuronal recovery.]

Clinical Neuroscience

[IMMOBILIZATION INDUCED FOS EXPRESSION IN THE MEDIAL AND LATERAL HYPOTHALAMIC AREAS: A LIMITED RESPONSE OF HYPOCRETIN NEURONS]

KISS Alexander

[Induction of Fos, a proto-oncogene c-fos protein product, was immunohistochemically examined in the rat hypothalamic neurons 3 h after a single (1×120 min) or repeated (7×120 min) immobilization (IMO) stress. The aim of the present study was to reveal a possible parallelism in the cell activation between the medial and lateral hypothalamic neurons, especially between the stress responsive neurons in the hypothalamic paraventricular nucleus (PVN) and hypocretin (Hcrt) synthesizing neurons, i.e. suspected stress active neurons of the lateral hypothalamus. After IMO, the animals were perfused and their brains processed with immunohistochemistry for Fos or Fos/Hcrt proteins. Acute IMO elicited extensive Fos expression in both the examined areas. Excessive Fos expression was mainly seen in the PVN, while Hcrt neurons failed to show a broad response (appr. 5%) to single IMO. Clear occurrence of Fos signal was also seen in both hypothalamic areas of IMO-habituated rats. However, in these animals, in both areas examined, the number of Fos neurons was considerably suppressed, including the PVN. These results indicate that IMO is able to evoke a concurrent activation of Fos in many medial and lateral hypothalamic neurons. However, the scanty response of Hcrt neurons to acute IMO does not allow to assort them to a distinct IMO stress-responsive neuronal phenotypes of the brain.]

Clinical Neuroscience

[PITUITARY ATRIAL NATRIURETIC PEPTIDE OF PARAVENTRICULAR NUCLEUS ORIGIN]

FODOR Mariann, MAKARA B. Gábor, PALKOVITS Miklós

[Atrial natriuretic peptide-synthesizing neurons in the hypothalamic paraventricular nucleus constitute the major sources of ANP in the three lobes of the pituitary gland. Complete transection of the pituitary stalk eliminated 93% of ANP from the intermediate lobe, 47 and 77% from the anterior and the posterior lobes, respectively. Meantime, increased levels of immunoreactive ANP were measured in the median eminence, due to the accumulation of the peptide in the transected axons centrally to the transected stalk and in the paraventricular nucleus. It is likely that ANP neurons in the paraventricular nucleus innervate the pituitary, but those in the periventricular (median) preoptic nucleus and the organum vasculosum laminae terminalis may not contribute to the ANP innervation of the pituitary gland.]

All articles in the issue

Related contents

Lege Artis Medicinae

[THE ROLE OF OBESITY IN GASTROENTEROLOGICAL DISEASES]

GYÖKERES Tibor, KIRÁLY Ágnes, LAKATOS László, MADÁCSY László

[This paper reviews the current knowledge on the association of obesity and gastrointestinal disorders. While the relationship between obesity and cardiovascular disorders has recently gained wide professional publicity, there are few data on the gastroenterological aspects of obesity. After a discussion on obesity as an epidemic, its international and national prevalence, and public health risks, the most common obesity-related gastrointestinal disorders, their incidence, pathomechanism and consequences are presented by the organ systems affected, including gastrooesophageal reflux disease, fatty liver, gallstone disease, diseases of the pancreas, and colorectal carcinoma. Finally, the means of prevention and treatment are summarized.]

Lege Artis Medicinae

[A new DPP-IV inhibitor: saxagliptin]

KIS János Tibor, MÉSZÁROS Gabriella

[Saxagliptin is a selective, potent inhibitor of dipeptidyl peptidase-IV (DPP-IV). By inhibiting DPP-IV, saxagliptin reduces the degradation of endogenous incretin hormones, resulting in increased glucose-dependent insulin and decreased glucagon secretion from the pancreas islets. Clinical trials of saxagliptin as monotherapy and as combination therapy with other oral antidiabetic medications including metformin, glibenclamide, glipizide, pioglitazone and rosiglitazone have demonstrated clinical benefits in different glycaemic endpoints. Due to its glucose- dependent mechanism of action, saxagliptin as monotherapy or in combination with metformin results in a very low risk for hypoglycemia. It has also been shown to be generally well-tolerated, with not having any relevant effect on weight. The authors summarize the most important saxagliptin trials.]

Hypertension and nephrology

[Treatment of high blood pressure in praxis and beyond. Hypertension praxis model]

ÁDÁM Ágnes

[Author presents a hypertension care model in the general praxis. Hypertensive patients and those with diabetes, hyperlipidemia and obesity, OSAS and the therapeutic results with these care model system for three years was analysed. The target blood pressure was achieved in a great rate in all patient’s groups. the elements of therapeutic success was analysed.]

Lege Artis Medicinae

[Sarcopenia – muscle loss – pathomechanism, clinical presentation and metabolic comorbidities]

VERECKEI Edit, HODINKA László

[Sarcopenia, or the age-related involution of muscle strength and muscle mass, is a serious public health concern, due to the growing number of elderly population caused by nowadays demographic changes i.e. prolonged life expectancy. By ageing, the muscle tissue is shrinking gradually, leading to the loss of muscle strength and masses. This condition is called sarcopenia. Sar­co­penia is the simultaneous decrease of muscle mass, muscle strength and functional independence. In parallel the physical performance deteriorates (weakness, slowness and poor physical balancing). Fatigue, el­derly behaviour and weight loss are the consequences of these accumulating deficits, which associate with cognitive decline and result in increasing social isolation. The primary form of sarcopenia is the decrease of the energy production of muscle cells and then the death of muscle cells. Se­con­dary, endocrine dysfunctions, diseases of the nervous system, decreased physical activity, malnutrition or malabsorption, chronic infection accelerate the process and aggravate the patient’s condition. Complex genetic, biochemical and endocrine mechanisms take part in the development of sarcopenia. This involution is due to the impaired balance of restoring and depleting processes of muscles. A questionnaire and algorithm have been developed to recognize, screen and diagnose the risks of sarcopenic condition; these separate the sarcopenic and non-sarcopenic patients with specific cut-off values. Sar­co­penia can be diagnosed based on walking speed, decreased handgrip strength and measured or calculated muscle mass in persons over 65. Sarcopenia can be considered as a phenomenon of “physiological” aging, however, it becomes a disease when diagnostic cut-offs are exceeded and the patient experiences functional disability and declining quality of life. Prevention and treatment of sarcopenia and reducing the risk of falling are based on regular active resistance and coordination exercises. Options for pharmaceutical treatments are limited since despite of identified molecular targets there are no convincingly effective innovative therapy on the horizon. Nevertheless, there are some weak evidence for efficacy of the application of amino acids stimulating muscle cell differentiation, such as leucine or the analogue of beta-hydoxy-methylbutyrate beside exercise therapy.]

Lege Artis Medicinae

[Connection between fetal development and adult diseases - Long acting effects of stress affecting the mother and the fetus]

MOLNÁR Ildikó

[The stress responses affecting the mother and the fetus have a life-long consequence in the manifestation of adult metabolic disorders. The perinatal stress inducing fetal adaptation contributes to alterations in tissue structures and hormone regulations as well as could lead to intrauterine growth retardation. The newborns with low birth weight are associated with the glucocorticoid, adrenaline and insulin resistance making them postnatal susceptible to obesity, diabetes type 2 and hypertonia. The number of newborns with low birth weight increase, therefore the prevention of adult diseases originating from perinatal misprogramming represents a frequent challenge for health services and society.]