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Trends in Endocrinology and Metabolism:... Feb 2017While the regulation of energy homeostasis by amylin is already well-characterized, emerging data suggest that amylin is also crucial for the development of neural... (Review)
Review
While the regulation of energy homeostasis by amylin is already well-characterized, emerging data suggest that amylin is also crucial for the development of neural pathways in the hypothalamus and caudal hindbrain (area postrema, AP; nucleus tractus solitarius, NTS). Exciting new findings demonstrate crucial amylin-leptin interactions in altering the activity of specific hypothalamic and AP neurons, and a role for amylin as a novel class of 'leptin sensitizers' which enhance leptin signaling in both leptin-sensitive and -resistant individuals, in part by stimulating IL-6 production by hypothalamic microglia. This review summarizes these findings and provides a hypothetical framework for future studies to elucidate the mechanisms by which amylin and leptin act individually and as co-conspirators to alter energy homeostasis and neuronal development.
Topics: Animals; Energy Metabolism; Homeostasis; Humans; Hypothalamus; Islet Amyloid Polypeptide; Leptin; Neurons; Signal Transduction
PubMed: 27938937
DOI: 10.1016/j.tem.2016.11.004 -
Neuroscience Nov 2020Amylin is co-secreted with insulin by pancreatic β-cells in response to a meal and produced by neurons in discrete hypothalamic brain areas. Leptin is proportionally... (Review)
Review
Amylin is co-secreted with insulin by pancreatic β-cells in response to a meal and produced by neurons in discrete hypothalamic brain areas. Leptin is proportionally secreted by the adipose tissue. Both hormones control food intake and energy homeostasis post-weaning in rodents. While amylin's main site of action is located in the area postrema (AP) and leptin's is located in the mediobasal hypothalamus, both hormones can also influence the other's signaling pathway; amylin has been shown enhance hypothalamic leptin signaling, and amylin signaling in the AP may rely on functional leptin receptors to modulate its effects. These two hormones also play major roles during other life periods. During pregnancy, leptin levels rise as a result of an increase in fat depot resulting in gestational leptin-resistance to prepare the maternal body for the metabolic needs during fetal development. The role of amylin is far less studied during pregnancy and lactation, though amylin levels seem to be elevated during pregnancy relative to insulin. Whether amylin and leptin interact during pregnancy and lactation remains to be assessed. Lastly, during brain development, amylin and leptin are major regulators of cell birth during embryogenesis and act as neurotrophic factors in the neonatal period. This review will highlight the role of amylin and leptin, and their possible interaction, during these dynamic time periods of pregnancy, lactation, and early development.
Topics: Amyloid; Child Development; Female; Humans; Infant, Newborn; Islet Amyloid Polypeptide; Lactation; Leptin; Pregnancy; Receptors, Leptin
PubMed: 31846753
DOI: 10.1016/j.neuroscience.2019.11.034 -
International Journal of Molecular... Jan 2024Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term-diabesity-has... (Review)
Review
Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term-diabesity-has emerged. The gut-brain axis plays a critical function in maintaining glucose and energy homeostasis and involves a variety of peptides. Amylin is a neuroendocrine anorexigenic polypeptide hormone, which is co-secreted with insulin from β-cells of the pancreas in response to food consumption. Aside from its effect on glucose homeostasis, amylin inhibits homeostatic and hedonic feeding, induces satiety, and decreases body weight. In this narrative review, we summarized the current evidence and ongoing studies on the mechanism of action, clinical pharmacology, and applications of amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders, such as obesity.
Topics: Humans; Islet Amyloid Polypeptide; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Insulin; Obesity; Glucose; Amyloid
PubMed: 38338796
DOI: 10.3390/ijms25031517 -
Physiology & Behavior Aug 2020The intake- and body weight-suppressive hormone amylin exerts effects on energy balance control at a variety of nuclei within the brain, including sites that have been... (Review)
Review
The intake- and body weight-suppressive hormone amylin exerts effects on energy balance control at a variety of nuclei within the brain, including sites that have been referred to in the literature as mediating homeostatic versus hedonic aspects of feeding. Here, we review key central nervous system sites of action for amylin signaling in the neural control of feeding and body weight, and discuss how these sites may interact to mediate the effects of amylin within the brain. Additionally, we review recent findings suggesting that amylin influences alcohol intake, suggesting broader effects of amylin on motivated behavior beyond feeding.
Topics: Body Weight; Eating; Energy Metabolism; Humans; Islet Amyloid Polypeptide; Receptors, Islet Amyloid Polypeptide; Signal Transduction
PubMed: 32439326
DOI: 10.1016/j.physbeh.2020.112958 -
Frontiers in Endocrinology 2020The hormones amylin and calcitonin interact with receptors within the same family to exert their effects on the human organism. Calcitonin, derived from thyroid C cells,... (Review)
Review
The hormones amylin and calcitonin interact with receptors within the same family to exert their effects on the human organism. Calcitonin, derived from thyroid C cells, is known for its inhibitory effect on osteoclasts. Calcitonin of mammalian origin promotes insulin sensitivity, while the more potent calcitonin extracted from salmon additionally inhibits gastric emptying, promotes gallbladder relaxation, increases energy expenditure and induces satiety as well as weight loss. Amylin, derived from pancreatic beta cells, regulates plasma glucose by delaying gastric emptying after meal ingestion, and modulates glucagon secretion and central satiety signals in the brain. Thus, both hormones seem to have metabolic effects of relevance in the context of non-alcoholic fatty liver disease (NAFLD) and other metabolic diseases. In rats, studies with dual amylin and calcitonin receptor agonists have demonstrated robust body weight loss, improved glucose tolerance and a decreased deposition of fat in liver tissue beyond what is observed after a body weight loss. The translational aspects of these preclinical data currently remain unknown. Here, we describe the physiology, pathophysiology, and pharmacological effects of amylin and calcitonin and review preclinical and clinical findings alluding to the future potential of amylin and calcitonin-based drugs for the treatment of obesity and NAFLD.
Topics: Amylin Receptor Agonists; Animals; Body Weight; Calcitonin; Diet, High-Fat; Fatty Liver; Humans; Islet Amyloid Polypeptide; Obesity
PubMed: 33488526
DOI: 10.3389/fendo.2020.617400 -
Physiology & Behavior Aug 2016Amylin, a peptide hormone produced in the pancreas and in the brain, has well-established physiological roles in glycemic regulation and energy balance control. It... (Review)
Review
Amylin, a peptide hormone produced in the pancreas and in the brain, has well-established physiological roles in glycemic regulation and energy balance control. It improves postprandial blood glucose levels by suppressing gastric emptying and glucagon secretion; these beneficial effects have led to the FDA-approved use of the amylin analog pramlintide in the treatment of diabetes mellitus. Amylin also acts centrally as a satiation signal, reducing food intake and body weight. The ability of amylin to promote negative energy balance, along with its unique capacity to cooperatively facilitate or enhance the intake- and body weight-suppressive effects of other neuroendocrine signals like leptin, have made amylin a leading target for the development of novel pharmacotherapies for the treatment of obesity. In addition to these more widely studied effects, a growing body of literature suggests that amylin may play a role in processes related to cognition, including the neurodegeneration and cognitive deficits associated with Alzheimer's disease (AD). Although the function of amylin in AD is still unclear, intriguing recent reports indicate that amylin may improve cognitive ability and reduce hallmarks of neurodegeneration in the brain. The frequent comorbidity of diabetes mellitus and obesity, as well as the increased risk for and occurrence of AD associated with these metabolic diseases, suggests that amylin-based pharmaceutical strategies may provide multiple therapeutic benefits. This review will discuss the known effects of amylin on glycemic regulation, energy balance control, and cognitive/motivational processes. Particular focus will be devoted to the current and/or potential future clinical use of amylin pharmacotherapies for the treatment of diseases in each of these realms.
Topics: Animals; Appetite Depressants; Blood Glucose; Cognition; Energy Metabolism; Humans; Islet Amyloid Polypeptide
PubMed: 26922873
DOI: 10.1016/j.physbeh.2016.02.034 -
The Diabetes Educator Dec 2015The pathophysiology of diabetes has historically focused on alterations in insulin secretion and function; however, diabetes involves multiple hormonal alterations,... (Review)
Review
PURPOSE
The pathophysiology of diabetes has historically focused on alterations in insulin secretion and function; however, diabetes involves multiple hormonal alterations, including abnormal regulation of amylin. This review discusses the physiologic functions of amylin in glucose homeostasis and the rationale for amylin replacement in type 1 and 2 diabetes. The use of pramlintide, a synthetic amylin analog, is also discussed.
CONCLUSIONS
Amylin, formed primarily in pancreatic islet β cells, is cosecreted with insulin in response to caloric intake. Patients with type 1 diabetes have lower baseline amylin serum concentrations, and amylin response to caloric intake is absent. Patients with type 2 diabetes requiring insulin also have a diminished amylin response to caloric intake, potentially related to the degree of β-cell impairment. Key physiologic functions of amylin in maintaining glucose homeostasis include suppressing glucagon release in response to caloric intake, delaying the rate of gastric emptying, and stimulating the satiety center in the brain to limit caloric intake. Pramlintide is indicated for adults with type 1 and 2 diabetes who have not achieved adequate glucose control despite optimal insulin therapy. As an adjunct to insulin therapy, pramlintide demonstrated significant reductions in A1C in patients with type 1 and 2 diabetes, with favorable effects on body weight. It is administered subcutaneously before each major meal. There is an increased risk of hypoglycemia with insulin when used in combination with pramlintide. Other adverse effects may include nausea, vomiting, anorexia, reduced appetite, and headache. Proper patient selection and education are essential to successful pramlintide use.
Topics: Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Homeostasis; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Islet Amyloid Polypeptide
PubMed: 26424675
DOI: 10.1177/0145721715607642 -
Physiology & Behavior Sep 2014Amylin is a pancreas-derived neuropeptide that acts in the central nervous system (CNS) to reduce food intake. Much of the literature describing the anorectic effects of... (Review)
Review
Amylin is a pancreas-derived neuropeptide that acts in the central nervous system (CNS) to reduce food intake. Much of the literature describing the anorectic effects of amylin are focused on amylin's actions in the area postrema, a hindbrain circumventricular structure. Although the area postrema is certainly an important site that mediates the intake-suppressive effects of amylin, several pieces of evidence indicate that amylin may also promote negative energy balance through action in additional CNS nuclei, including hypothalamic and mesolimbic structures. Therefore, this review highlights the distributed neural network mediating the feeding effects of amylin signaling with special attention being devoted to the recent discovery that the ventral tegmental area is physiologically relevant for amylin-mediated control of feeding. The production of amylin by alternative, extra-pancreatic sources and its potential relevance to food intake regulation is also considered. Finally, the utility of amylin and amylin-like compounds as a component of combination pharmacotherapies for the treatment of obesity is discussed.
Topics: Animals; Appetite Regulation; Central Nervous System; Eating; Energy Metabolism; Humans; Islet Amyloid Polypeptide; Obesity
PubMed: 24480072
DOI: 10.1016/j.physbeh.2014.01.013 -
Frontiers in Bioscience (Landmark... Jun 2014Metabolic syndrome significantly increases the incidence of atherosclerosis-related diseases including coronary artery disease, stroke, and type 2 diabetes. Recent... (Review)
Review
Metabolic syndrome significantly increases the incidence of atherosclerosis-related diseases including coronary artery disease, stroke, and type 2 diabetes. Recent progress has demonstrated that amylin, or islet amyloid polypeptide, is circulating multifunctional hormone and neuropeptide, which is co-secreted with insulin into the bloodstream by pancreatic beta cells and plays a very important role in regulating feeding, energy homeostasis and inflammation. Recent FDA approval of amylin analog pramlintide as a new drug for treating type 1 and 2 diabetes positions amylin in the spotlight. In this analytical review, I summarize the recent progress on amylin studies in the following sections: 1) introduction to the molecular features of amylin; 2) amylin's amyloidogenic and proinflammatory effects; 3) a satiety hormone and new drug in increasing energy expenditure; and 4) a vasodilator inducing hypotension and tachycardia; and 5) a neuropeptide in depolarizing cholinergic neurons via closure of potassium channels. Continued improvement of our understanding on this multifunctional hormone would lead to future development of pramlintide as novel therapies for other inflammatory, hematological, metabolic, neurological and vascular diseases.
Topics: Brain; Cholinergic Neurons; Energy Metabolism; Humans; Hypoglycemic Agents; Inflammation; Islet Amyloid Polypeptide; Membrane Potentials; Vasodilation
PubMed: 24896327
DOI: 10.2741/4258 -
Current Protein & Peptide Science Jun 2013Amylin (islet amyloid polypeptide) and amyloid beta protein (Aβ), identified as proteinaceous deposits within the pancreas of diabetics and the brain of Alzheimer's... (Review)
Review
Amylin (islet amyloid polypeptide) and amyloid beta protein (Aβ), identified as proteinaceous deposits within the pancreas of diabetics and the brain of Alzheimer's patients respectively, share many biophysical, physiological and neurotoxic properties. Although no specific β receptor" has been identified, emerging evidence suggests that the amylin receptor serves a putative target receptor for the actions of Aβ in the brain. The amylin receptor consists of a calcitonin receptor dimerized with receptor activity-modifying proteins and is widely distributed within central nervous system. Aβ can directly activate this G protein-coupled receptor and trigger multiple intracellular signal transduction messengers and pathways that include calcium, cAMP, ERK1/2 and Fos. Growing evidence suggests that amylin and amylin receptors are involved in many aspects of neurodegenerative pathophysiology. Developing therapeutic strategies aimed at modulating amylin receptor function may prove useful for treatment of neurodegenerative diseases such as Alzheimer's disease.
Topics: Amyloid beta-Peptides; Animals; Cell Death; Central Nervous System; Humans; Islet Amyloid Polypeptide; Neurodegenerative Diseases; Neurons; Receptors, Islet Amyloid Polypeptide; Signal Transduction
PubMed: 23745698
DOI: 10.2174/13892037113149990051