Insulin degradation by adipose tissue is increased in human obesity

White adipose tissue samples from obese and lean patients were used for the estimation ofinsulin protease and insulin:glutathione transhydrogenase using 1251-labeled insulin. There was no activity detected in the absence of reduced glutathione, which indicates that insulin is cleaved in human adipose "tissue through reduction of the disulfide bridge between the chains. O bese patients showed higher transhydrogenase activity (per U tissue protein wt, per U tissue wt, and in the total adipose tissue mass) than the lean group. There is a significant correlation between the activity per U tissue wt, and protein and total activity in the whole adipose tissue with respect to body mass index, with a higher activity in obese patients. The potential ofinsulin cleavage by adipose tissue in obese patients was a mean 5.6-fold higher than that in controla. The coexistence of high insulinemia and high cleavage capability implies that insulin secretion and turnover are increased in the o bese. Thus, white adipose tissue may be crucial in the control of energy availability through modulation ofinsulin cleavage

Methods in the treatment of obesity

L'obesitat és una malaltia molt estesa que Iimita I'activitat i escurça Ia vida, i que es pot definir com un mmagatzemament patològic de reserves de greix. Malgrat Ia difusió epidèmica, no hi ha cap sistema plenament efectiu disponible per tractar-Ia. Les estratègies emprades per al tractament de I'obesitat s'han basat principalment en Ia Iimitació de Ia ingesta i/o l'increment de Ia despesa energètica. EI mètode més emprat per Iimitar Ia ingesta energètica ha estat Ia utilització de dietes hipocalòriques, però l'efectivitat és Iimitada i es perd ràpidament amb el temps. Malgrat això, Ia utilització adequada de dietes hipocalòriques constitueix encara el principal procediment en Ia Iluita contra el sobrepès. També s'ha emprat el bloqueig de I'absorció de nutrients mitjançant Ia inhibició específica d'enzims digestius. La cirurgia bariàtrica és ara pràcticament I'únic mètode prou efectiu per tractar els obesos mòrbids. S'ha utilitzat el condicionament conductista per mantenir els obesos allunyats del menjar, però els resultats són sovint poc satisfactoris. No obstant això, Ia informació adequada que reben els obesos sobre els principis elementals de Ia nutrició, així com Ia reeducació nutricional són una eina que no s'ha de deixar de costat. L'exercici és Ia forma més senzilla d'augmentar Ia despesa energètica i, tot i que aquest increment és sols transitori, potencia els efectes aprimadors de Ia restricció dietètica. Hi ha un nombre considerable de fàrmacs que han estat emprats per al tractament de I'obesitat i encara n'hi ha més que estan essent estudiats i desenvolupats. EI principal objectiu d'aquests fàrmacs és disminuir Ia gana a fi d'ajudar I'obès a reduir la quantitat de menjar, però altres drogues tendeixen a incrementar Ia termogènesi, tot facilitant Ia utilització de Ies reserves grasses; sovint ambdós efectes tenen lloc a l'hora. les drogues més àmpliament estudiades són Ies serotoninèrgiques, que actuen sobre e cervell, i els agents adrenèrgics que actuen sobre Ia gana i Ia producció de calor. Diverses hormones, metabòlits i fins I tot verins han estat postulats pee al tractament de I'obesitat, però ara per ara Ies àrees d'estudi amb més possibilitats de futur són Ies basades en el control hipotalàmic de Ia gana, Ia termogènesi i el control regulador de Ia massa de greix mitjançant molècules senyal produïdes pel propi teixit adipós. S'han investigat moltes vies per trobar formes efectives per tractar I'obesitat, però Ia major part dels esforços encara es- obesity tan orientats a trobar solucions parcials al complex problema de l'obesitat. L'esforç coordinat en recerca bàsica i el desenvolupament de fàrmacs efectius, junt amb una adequada informació als pacients i I'actualització dels coneixements del personal sanitari que treballa en aquest camp, són les condicions essencials per poder fer front a aquesta malaltia perillosa que s'estén d'una manera incontrolada: I'obesitat.Obesity is a widespread crippling and life-shortening disease that can be defined as a pathologic accumulation of fat reserves. In spite of its epidemic distribution, no fully effective treatments are available. The strategies used for the treatment of obesity have relied mainly on the limitation of energy intake or/and increasing energy expenditure. The most widely used method to limit energy intake has been the use of hypocaloric diets. Their effectivity is limited and fade away rapidly with time. Nevertheless, the sound use of hypocaloric diets is yet the mainstay of the fight against overweight. Inhibition of the absorption of nutrients through specific digestive enzyme inhibitors has been also used. Bariatric surgery is now practically the only fairly effective way to treat the morbidly obese. Conductist conditioning has been used to maintain the obese as far as possible from food, but the results are often poor. However, adequate instruction of the obese on basic nutritional knowledge, and nutritional reeducation are a tool not to be neglected. Exercise is the easiest way to increase energy expenditure. But this increase is only transient; in any case it potentiates the slimming effects of dietary restriction. There are a growing number of drugs used for the treatment of obesity, and more are just being under study and development. The main target of these drugs is to diminish the cravings of appetite as a way to help the obese to limit ingestion, but other drugs tend to increase thermogenesis, easing the consumption of fat reserves; often both effects add up. The most widely studied drugs are serotonergic drugs acting on the brain and adrenergic agents acting both on appetite and heat production. Several hormones, metabolites and even poisons have been postulated as antiobesity agents, but now the most promising areas of study rely on hypothalamic control of appetite, thermogenesis and regulatory control of the mass of fat, the latter achieved through signalling molecules produced by the adipose tissue. Many avenues have been probed to try to find an effective way to treat obesity. However, most of the efforts are yet focussed on the development of partial solutions to the complex problem of obesity. Coordinated effort of basic research, and the development of effective drugs together with adequate information of the patients and actualization of the knowledge of the health personnel working in the field are needed to face the threat of dangerous and uncontrollably spreading obesit

Insulin degradation by adipose tissue is increased in human obesity

White adipose tissue samples from obese and lean patients were used for the estimation ofinsulin protease and insulin:glutathione transhydrogenase using 1251-labeled insulin. There was no activity detected in the absence of reduced glutathione, which indicates that insulin is cleaved in human adipose "tissue through reduction of the disulfide bridge between the chains. O bese patients showed higher transhydrogenase activity (per U tissue protein wt, per U tissue wt, and in the total adipose tissue mass) than the lean group. There is a significant correlation between the activity per U tissue wt, and protein and total activity in the whole adipose tissue with respect to body mass index, with a higher activity in obese patients. The potential ofinsulin cleavage by adipose tissue in obese patients was a mean 5.6-fold higher than that in controla. The coexistence of high insulinemia and high cleavage capability implies that insulin secretion and turnover are increased in the o bese. Thus, white adipose tissue may be crucial in the control of energy availability through modulation ofinsulin cleavage