Oral Salmon Calcitonin Improves Fasting and Postprandial Glycemic Control in Lean Healthy Rats

Feigh, Michael; Nielsen, Rasmus Hjorth; Hansen, Christina; Henriksen, Kim; Christiansen, Claus; Karsdal, Morten A.

doi:10.1055/s-0031-1298027

Cited by 11 publications

(7 citation statements)

References 10 publications

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“…In previous studies, we reported that a CTR allele is one of the genetic factors regulating human body weight 41 ; this may be strongly associated with the present results. A therapeutic dose of CT reduces food intake and body weight in rats 11 – 13 , 42 – 44 . However, we found no significant differences in daily food intake between WT and KO mice, although KO mice had reduced body weight compared to WT in the present study.…”

Section: Discussionmentioning

confidence: 99%

Endogenous calcitonin regulates lipid and glucose metabolism in diet-induced obesity mice

Nakamura

Nomura

Yamakawa

et al. 2018

Sci Rep

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Calcitonin (CT) plays an important role in calcium homeostasis, and its precursor, proCT, is positively associated with the body mass index in the general human population. However, the physiological role of endogenous CT in the regulation of metabolism remains unclear. Knockout mice with gene-targeted deletion of exon 4 of Calca (CT KO) were generated by targeted modification in embryonic stem cells. Male mice were used in all experiments and were fed a slightly higher fat diet than the standard diet. The CT KO mice did not exhibit any abnormal findings in appearance, but exhibited weight loss from 15 months old, i.e., significantly decreased liver, adipose tissue, and kidney weights, compared with wild-type control mice. Furthermore, CT KO mice exhibited significantly decreased fat contents in the liver, lipid droplets in adipose tissues, serum glucose, and lipid levels, and significantly increased insulin sensitivity and serum adiponectin levels. CT significantly promoted 3T3-L1 adipocyte differentiation and suppressed adiponectin release. These results suggested that CT gene deletion prevents obesity, hyperglycemia, and hyperlipidemia in aged male mice. This is the first definitive evidence that CT may contribute to glucose and lipid metabolism in aged male mice, possibly via decreased adiponectin secretion from adipocytes.

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Section: Discussionmentioning

confidence: 99%

Endogenous calcitonin regulates lipid and glucose metabolism in diet-induced obesity mice

Nakamura

Nomura

Yamakawa

et al. 2018

Sci Rep

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“…In the present study, oral sCT treatment exerted amylin‐like effects by inducing a pronounced reduction in postprandial glycaemia during OGTT in ZDF rats, as also recently demonstrated in lean healthy and diet‐induced obese rats (Feigh et al ., 2011; 2012). Although the effects of oral sCT upon gastric emptying were not measured directly, the pronounced reduction in glucose excursion during the initial phase following glucose administration during OGTT, but not IPGTT, do suggest a mode of action involving glucose absorption from the GI tract.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, male ZDF rats, an animal model of type 2 diabetes, were used to evaluate the effects of oral sCT treatment on glycaemic control, pancreatic and incretin hormonal profiles and pancreatic beta-cell morphology; we extended previous studies on the beneficial influence of oral sCT on glucose homeostasis in lean healthy and diet-induced obese rats (Feigh et al, 2011;2012). We demonstrated that oral sCT dose-dependently attenuates the development of hyperglycaemia in severely diabetic ZDF rats as observed by reductions in fasting and non-fasted blood glucose and HbA1C.…”

Section: Discussionmentioning

confidence: 99%

Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta‐cell area and function in Zucker diabetic fatty rats

Feigh

Andreassen

Neutzsky-Wulff

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSE Oral salmon calcitonin (sCT), a dual‐action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet‐induced obese rats. Here, we have evaluated the anti‐diabetic efficacy of oral sCT using parameters of glycaemic control and beta‐cell morphology in male Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. EXPERIMENTAL APPROACH Male ZDF rats were treated with oral sCT (0.5, 1.0 or 2 mg·kg−1) or oral vehicle twice daily from age 8 to 18 weeks. Zucker lean rats served as control group. Fasting and non‐fasted blood glucose, glycosylated haemoglobin (HbA1c) and levels of pancreas and incretin hormones were determined. Oral glucose tolerance test and i.p. glucose tolerance test were compared, and beta‐cell area and function were evaluated. KEY RESULTS Oral sCT treatment dose‐dependently attenuated fasting and non‐fasted hyperglycaemia during the intervention period. At the end of the study period, oral sCT treatment by dose decreased diabetic hyperglycaemia by ∼9 mM and reduced HbA1c levels by 1.7%. Furthermore, a pronounced reduction in glucose excursions was dose‐dependently observed for oral sCT treatment during oral glucose tolerance test. In addition, oral sCT treatment sustained hyperinsulinaemia and attenuated hyperglucagonaemia and hypersecretion of total glucagon‐like peptide‐1 predominantly in the basal state. Lastly, oral sCT treatment dose‐dependently improved pancreatic beta‐cell function and beta‐cell area at study end. CONCLUSIONS AND IMPLICATIONS Oral sCT attenuated diabetic hyperglycaemia in male ZDF rats by improving postprandial glycaemic control, exerting an insulinotropic and glucagonostatic action in the basal state and by preserving pancreatic beta‐cell function and beta‐cell area.

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“…Given its clinical usage, it is unsurprising that salmon CT has been explored as a treatment for other disorders. Numerous studies have suggested that salmon CT could treat metabolic disorders by lowering body weight, elevating energy expenditure, limiting food intake and improving glucose handling in rats (Lutz et al, ; Eiden et al, ; Wielinga et al, ; Feigh et al, ; ). Recently, a number of CT mimetics, known by ‘KBP’ codes, for example, KBP‐042, KBP‐088 and KBP‐089, have been described (Patent WO 2015/071229).…”

Section: Developments With Agonistsmentioning

confidence: 99%

Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25

Hay

Garelja

Poyner

et al. 2017

British J Pharmacology

311

441

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The calcitonin/CGRP family of peptides includes calcitonin, α and β CGRP, amylin, adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD). Their receptors consist of one of two GPCRs, the calcitonin receptor (CTR) or the calcitonin receptor-like receptor (CLR). Further diversity arises from heterodimerization of these GPCRs with one of three receptor activity-modifying proteins (RAMPs). This gives the CGRP receptor (CLR/RAMP1), the AM and AM receptors (CLR/RAMP2 or RAMP3) and the AMY AMY and AMY receptors (CTR/RAMPs1-3 complexes, respectively). Apart from the CGRP receptor, there are only peptide antagonists widely available for these receptors, and these have limited selectivity, thus defining the function of each receptor in vivo remains challenging. Further challenges arise from the probable co-expression of CTR with the CTR/RAMP complexes and species-dependent splice variants of the CTR (CT and CT ). Furthermore, the AMY receptor is activated equally well by both amylin and CGRP, and the preferred receptor for AM2/IMD has been unclear. However, there are clear therapeutic rationales for developing agents against the various receptors for these peptides. For example, many agents targeting the CGRP system are in clinical trials, and pramlintide, an amylin analogue, is an approved therapy for insulin-requiring diabetes. This review provides an update on the pharmacology of the calcitonin family of peptides by members of the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology and colleagues.

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Oral Salmon Calcitonin Improves Fasting and Postprandial Glycemic Control in Lean Healthy Rats

Cited by 11 publications

References 10 publications

Endogenous calcitonin regulates lipid and glucose metabolism in diet-induced obesity mice

Endogenous calcitonin regulates lipid and glucose metabolism in diet-induced obesity mice

Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta‐cell area and function in Zucker diabetic fatty rats

Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25

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