BZ043, a novel long-acting amylin analog, reduces gastric emptying, food intake, glycemia and insulin requirement in streptozotocin-induced diabetic rats

Nascimento, Caio Victor M. F. do; Sinézia, Celimar; Sisnande, Tháyna; Lima, L.M.T.R.; Lacativa, Paulo Gustavo Sampaio

doi:10.1016/j.peptides.2019.04.004

Cited by 13 publications

(6 citation statements)

References 40 publications

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“…With its short half-life, pramlintide therapy for weight loss was ultimately an unsuccessful strategy, requiring multiple daily injections to elicit little effect on body weight (83). Thus, prolonging the half-life of amylin and/or targeting both amylin and calcitonin receptors potentially makes amylinomimetic compounds more suitable for glucoregulatory purposes and weight loss therapy, and several such molecules have been developed (15,17,20,189,190,191,192,193,194). Davalintide was developed to overcome the short half-life and low bioavailability of pramlintide (189).…”

Section: Long-acting Amylin Analogues and Dual Agonistsmentioning

confidence: 99%

“…In both wildtype (WT) mice and rodent models of type 1 diabetes, a pegylated amylin analogue reduced meal-induced hyperglycaemia (190,197). The weightlowering ability of the selective long-acting amylin receptor agonist NN1213 compared to salmon calcitonin has been evaluated in mice maintained on a high-fat diet (191).…”

Section: Long-acting Amylin Analogues and Dual Agonistsmentioning

confidence: 99%

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THERAPY OF ENDOCRINE DISEASE: Amylin and calcitonin – physiology and pharmacology

Mathiesen

Lund

Holst

et al. 2022

European Journal of Endocrinology

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Type 2 diabetes is a common manifestation of metabolic dysfunction due to obesity and constitutes a major burden for modern health care systems, in concert with the alarming rise in obesity worldwide. In recent years, several successful pharmacotherapies improving glucose metabolism have emerged, and some of these also promote weight loss, thus, ameliorating insulin resistance. However, the progressive nature of type 2 diabetes is not halted by these new anti-diabetic pharmacotherapies. Therefore, novel therapies promoting weight loss further and delaying diabetes progression are needed. Amylin, a beta cell hormone, has satiating properties and it also delays gastric emptying and inhibits postprandial glucagon secretion with the net result of reducing postprandial glucose excursions. Amylin acts through the three amylin receptors, which have partial identity to the calcitonin receptor. Calcitonin, derived from thyroid C cells, is best known for its role in humane calcium metabolism, where it inhibits osteoclasts and reduces circulating calcium. However, calcitonin, particularly of salmon origin, has also been shown to affect insulin sensitivity, reduce gastric emptying rate and promote satiation. Pre-clinical trials with agents targeting the calcitonin receptor and the amylin receptors, which are based on the calcitonin core receptor, show improvements in several parameters of glucose metabolism including insulin sensitivity and some of these agents are currently undergoing clinical trials. Here, we review the physiological and pharmacological effects of amylin and calcitonin and discuss the future potential of amylin and calcitonin-based treatments for patients with type 2 diabetes and obesity.

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Section: Long-acting Amylin Analogues and Dual Agonistsmentioning

confidence: 99%

Section: Long-acting Amylin Analogues and Dual Agonistsmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Amylin and calcitonin – physiology and pharmacology

Mathiesen

Lund

Holst

et al. 2022

European Journal of Endocrinology

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“…In mice, subcutaneous administration of PEGylated amylin acutely reduces glycaemia with prolonged action compared to unmodified amylin ( 129 ). In rat models of type 1 diabetes, a PEGylated amylin analogue prevented meal-induced hyperglycaemia and promoted sustained normoglycaemia up to 8 h after injection of the amylin analogue ( 132 ). Importantly, acute and chronic studies show that long-acting amylin analogues decrease body weight and energy intake in rats ( 136 , 137 ).…”

Section: Amylin and Calcitonin-based Pharmacotherapiesmentioning

confidence: 99%

“…Amylin has been modified by various methods (e.g., by adding a polyethylene glycol (PEG), glycosylation, or albumin binding motif to the molecule) to extend its half-life and reduce the frequency of administration, thus making it more suitable for chronic use in body weight loss therapy (129)(130)(131)(132)(133)(134)(135). In mice, subcutaneous administration of PEGylated amylin acutely reduces glycaemia with prolonged action compared to unmodified amylin (129).…”

Section: Long-acting Amylin Agonistsmentioning

confidence: 99%

Amylin and Calcitonin: Potential Therapeutic Strategies to Reduce Body Weight and Liver Fat

et al. 2021

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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.

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“…[ 14 ] These features have recently been shown to be possible by bioconjugation of amylin with polyethylene glycol moieties, [ 23,24 ] resulting in stable combination with insulin and results in better outcomes for diabetes control over the use of insulin or amylin alone. [ 25–27 ]…”

Section: Introductionmentioning

confidence: 99%

Unambiguous characterization of PEGylation site on human amylin by two‐dimensional nuclear magnetic resonance spectroscopy

2021

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BZ043, a novel long-acting amylin analog, reduces gastric emptying, food intake, glycemia and insulin requirement in streptozotocin-induced diabetic rats

Cited by 13 publications

References 40 publications

THERAPY OF ENDOCRINE DISEASE: Amylin and calcitonin – physiology and pharmacology

THERAPY OF ENDOCRINE DISEASE: Amylin and calcitonin – physiology and pharmacology

Amylin and Calcitonin: Potential Therapeutic Strategies to Reduce Body Weight and Liver Fat

Unambiguous characterization of PEGylation site on human amylin by two‐dimensional nuclear magnetic resonance spectroscopy

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