Satiety

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

In clinical studies, selective DPP-4 inhibition increased active circulating concentrations of GLP-1 and GEP by two- to threefold. This was associated with increased glucose-induced insulin secretion and suppression of glucagon secretion, although changes in satiety and gastric emptying have not been repotted. 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Cholecystokinin (CCK) is produced in the intestine and the brain. It appears to be an important mediator of anxiety. It also stimulates vasopressin secretion and slows gastric emptying. In addition, it is an important humoral satiety signal (appetite control). Various antagonists have been developed and are currently being investigated with regard to their therapeutic potential. 

The paraventricular nucleus in the hypothalamus is located adjacent to the third ventricle and has been identified as a satiety center. Neurons in the paraventricular nucleus produce neuropeptides which inhibit feeding when injected into the brain (thyrotropinreleasing hormone (TRH), corticotropin-releasing hormone (CRH), oxytocin). 

Obviously, regulation of food intake depends on many neurotransmitters and hormones but this final section will outline the role played by central 5-HT transmission in this process. It had been the belief for some time that increased 5-HT transmission in the brain reduces food intake (Blundell 1977) and this certainly explains the satiety in rats that follows infusion of 5-HT into the paraventricular nucleus (PVN) of the hypothalamus. However, recent studies using microdialysis have found that 5-HT efflux in the lateral hypothalamus is itself increased by food intake, suggesting the existence of a feedback control system. In fact, because the increase in 5-HT efflux is greater in genetically obese rats than in their lean counterparts, it has been proposed that there is a deficiency in the 5-HT inhibition of food intake in obesity. 

Samanin, R and Grignaschi, G (1996) Role of 5-hydroxytryptamine receptor subtypes in satiety and animal models of eating disorders. In Drug Receptor Subtypes and Ingestive Behaviour (Eds Cooper, SJ and Clifton, PG), Academic Press, London, pp. 39-58. 

In addition to fiber and carbohydrate content, protein intake from legumes may have weight-loss benefits for obese individuals just because proteins enhance post-meal satiety (Rolls, 1995). However, a possible specific role for phytoestrogens in obesity has been postulated through the modulation of the satiety response, a neuroendocrine mechanism controlled by leptin (a hormone secreted by adipose tissue and already known to be regulated by... 

ROLLS B J (1995) Carbohydrates, fats and satiety. J Clin Nutr. 61 (4) 960S-967S. 

Patients may complain of swelling of their feet and ankles, which can extend up to their calves or thighs. Abdominal congestion may cause a bloated feeling, abdominal pain, early satiety, nausea, anorexia, and constipation. Often patients may have difficulty fitting into their shoes or pants due to edema. 

Gastric outlet obstruction occurs in approximately 2% of patients with PUD and is usually caused by ulcer-related inflammation or scar formation near the peripyloric region. Signs and symptoms of outlet obstruction include early satiety after meals, nausea, vomiting, abdominal pain, and weight loss. Ulcer healing with conventional acid-suppressive therapy is the primary treatment, but if this is unsuccessful then an endoscopic procedure (e.g., balloon dilation) is required. 

Patients with ascites may complain of abdominal pain, nausea, increasing tightness and fullness in the abdomen, shortness of breath and early satiety. 

Gastrointestinal complications (e.g., nausea, vomiting, early satiety, constipation, and diarrhea)... 

Sibutramine and its two active metabolites (Mj and M2) exert their effect by inhibiting the reuptake of serotonin, norepinephrine, and dopamine.29 Appetite becomes suppressed because patients feel a sense of satiety. 

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