Abstract Objective: Dual amylin and calcitonin receptor agonists (DACRAs) are novel therapeutic agents that not only improve insulin sensitivity but also work as an adjunct to established T2DM therapies. DACRAs are currently administered once daily, though it is unknown whether DACRAs with increa...
June 29, 2021
Journal:
Molecular Metabolism
Author:
K V Andreassen, A T Larsen, N Sonne, K E Mohamed, M A Karsdal, K Henriksen
Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time...
May 4, 2020
Journal:
J Pharmacol Exp Ther
Author:
Larsen AT, Sonne N, Andreassen KV, Karsdal MA, Henriksen K
Amylin treatment improves body weight and glucose control, although it is limited by a short action and need for high doses. Dual amylin and calcitonin receptor agonists (DACRAs) are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to what extent ...
April 21, 2020
Journal:
J Pharmacol Exp Ther
Author:
Larsen AT, Sonne N, Andreassen KV, Karsdal MA, Henriksen K
Pharmacological treatment with dual amylin and calcitonin receptor agonists (DACRAs) cause significant weight loss and improvement of glucose homeostasis. In this study, the maximally efficacious dose of the novel DACRA, KeyBiosciencePeptide (KBP)-066, was investigated. Two different rat models were...
April 14, 2020
Journal:
J Pharmacol Exp Ther
Author:
Sonne N, Larsen AT, Andreassen KV, Karsdal MA, Henriksen K
KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of ...
July 1, 2019
Journal:
J Pharmacol Exp Ther
Author:
Larsen AT, Sonne N, Andreassen KV, Gehring K, Karsdal MA, Henriksen K
OBJECTIVE: This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Patients with T2DM (n = 191) underwent an or...
July 1, 2019
Journal:
Diabetes Care
Author:
Bril F, Leeming DJ, Karsdal MA, Kalavalapalli S, Darb D, Lai J, Rabe M, Cusi K
BACKGROUND: Biomarkers that predict response to anabolic therapies could expedite the development of function promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM). METHODS: Ser...
May 23, 2019
Journal:
J Clin Endocrinol Metab
Author:
Huang G, Rocha GV, Pencina KM, Cox K, Krishnan V, Henriksen K, Mitchell P, Sissons SE, Li Z, Nedergaard AF, Karsdal MA, Sun S, Storer TW, Basaria S, Bhasin S
OBJECTIVE: Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI for...
April 11, 2018
Journal:
Diabetes Care
Author:
Rasmussen DGK, Hansen TW, von Scholten BJ, Nielsen SH, Reinhard H, Parving HH, Tepel M, Karsdal MA, Jacobsen PK, Genovese F, Rossing P
Dementia and type 2 diabetes are both characterized by long prodromal phases, challenging the study of potential risk factors and their temporal relation. The progressive relation among metabolic syndrome, insulin resistance (IR), and dementia has recently been questioned, wherefore the aim of this ...
April 7, 2017
Journal:
Diabetes Care
Author:
Neergaard JS, Dragsbæk K, Christiansen C, Nielsen HB, Brix S, Karsdal MA, Henriksen K
OBJECTIVE: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 µg/kg-10 µg/kg) compared with saline-treated and pair-fed controls. METHODS: Rats with obesity received daily s.c. admi...
August 1, 2016
Journal:
Br J Clin Pharmacol
Author:
Hjuler ST, Gydesen S, Andreassen KV, Pedersen SL, Hellgren LI, Karsdal MA, Henriksen K
This study aims to elucidate the mechanism behind the potent weight loss induced by dual amylin and calcitonin receptor agonists (DACRA) through comparison of the novel DACRA KBP-088 with the amylinomimetic davalintide with regard to in vitro receptor pharmacology and in vivo efficacy on food intake...
May 1, 2016
Journal:
Am J Physiol Endocrinol Metab
Author:
Gydesen S, Hjuler ST, Christensen JM, Karsdal MA, Arbit E, Andreassen KV
This study aims to elucidate the mechanism behind the potent weight loss induced by dual amylin and calcitonin receptor agonists (DACRA) through comparison of the novel DACRA KBP-088 with the amylinomimetic davalintide with regard to in vitro receptor pharmacology and in vivo efficacy on food intake...
May 1, 2016
Journal:
Am J Physiol Endocrinol Metab
Author:
Gydesen S, Hjuler ST, Christensen JM, Karsdal MA, Arbit E, Andreassen KV
BACKGROUND:Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers ...
December 7, 2015
Journal:
PLoS One
Author:
Sun S, Henriksen K, Karsdal MA, Byrjalsen I, Rittweger J, Armbrecht G, Belavý DL, Felsenbeg D, Nedergaard AF
BACKGROUND:Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers ...
December 7, 2015
Journal:
PLoS One
Author:
Sun S, Henriksen K, Karsdal MA, Byrjalsen I, Rittweger J, Armbrecht G, Belavý DL, Felsenbeg D, Nedergaard AF
BACKGROUND:Loss of muscle mass and function is an important complication to ageing and a range of pathologies, including, but not restricted to, cancer, organ failures, and sepsis. A number of interventions have been proposed ranging from exercise to anabolic pharmacological therapy, with varying su...
December 6, 2015
Journal:
J Cachexia Sarcopenia Muscle
Author:
Nedergaard A, Dalgas U, Primdahl H, Johansen J, Overgaard J, Overgaard K, Henriksen K, Karsdal MA, Lønbro S
KBP-042 is a synthetic peptide dual amylin- and calcitonin-receptor agonist (DACRA) developed to treat type 2 diabetes by inducing a significant weight loss while improving glucose homeostasis. In this study the aim was to compare two different formulations: An oral formulation (1mg/kg) to subcutane...
September 5, 2015
Journal:
Eur J Pharmacol
Author:
Hjuler ST, Andreassen KV, Gydesen S, Karsdal MA, Henriksen K
The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken t...
May 1, 2015
Journal:
Br J Clin Pharmacol
Author:
Karsdal MA, Riis BJ, Mehta N, Stern W, Arbit E, Christiansen C, Henriksen K
We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present st...
May 22, 2014
Journal:
Eur J Pharmacol
Author:
Michael Feigh, Kim V Andreassen, Sofie Gydesen, Ida Ottosen, Jan Erik Henriksen, Henning Beck-Nielsen, Claus Christiansen, Morten A Karsdal, Kim Henriksen
Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c).Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are ...
October 30, 2012
Journal:
J Transl Med.
Author:
Anita V Neutzsky-Wulff Kim V Andreassen, Sara T Hjuler, Michael Feigh, Anne-Christine Bay-Jensen, Qinlong Zheng, Kim Henriksen, Morten A Karsdal
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