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
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
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
KBP-042 is a dual amylin and calcitonin receptor agonist that increases glucose tolerance and insulin action and reduces body weight in rat models of obesity and prediabetes. The objective of the present study was to 1) evaluate KBP-042 as a treatment of late-stage type 2 diabetes in a rat model and...
April 24, 2017
Journal:
J Pharmacol Exp Ther
Author:
Hjuler ST, Gydesen S, Andreassen KV, Karsdal MA, Henriksen K
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, Brix S, Karsdal MA, Henriksen K, Nielsen Bay H
Background: Hyperglycaemia increases the risk of type 2 diabetes, heart disease and stroke, and is influenced by weight. However, the impact of preceding weight change on blood glycemia levels in late-life is less well understood. Aim: We studied the interplay between weight change and risk of hype...
March 6, 2017
Journal:
Aging Clin Exp Res
Author:
Dragsbæk K, Neergaard JS, Christiansen C, Karsdal MA, Beck-Nielsen H, Brix S, Henriksen K
Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study we investigated how to optimize tolerability while maintaining efficacy of a novel, highly potent dual amylin and calcitonin receptor agonist (DACRA), KBP-089. Furtherm...
January 21, 2017
Journal:
Br J Clin Pharmacol
Author:
Gydesen S, Hjuler ST, Freving Z, Andreassen KV, Sonne N, Hellgren LI, Karsdal MA, Henriksen K
There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria...
October 20, 2016
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Karsdal MA, Henriksen K, Nielsen MJ, Byrjalsen I, Leeming DJ, Gardner SD, Goodman ZD, Patel K, Krag A, Christiansen C, Schuppan D
The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) a...
September 15, 2016
Journal:
Medicine (Baltimore)
Author:
Dragsbæk K", Neergaard JS, Laursen JM, Hansen HB, Christiansen C, Beck-Nielsen H, Karsdal MA, Brix S, Henriksen K
AIMS/HYPOTHESIS:The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of proco...
September 8, 2016
Journal:
Diabetologia
Author:
Karsdal MA, Henriksen K, Genovese F, Leeming DJ, Nielsen MJ, Riis BJ, Christiansen C, Byrjalsen I, Schuppan D
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
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
The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced obes...
May 6, 2014
Journal:
Am J Physiol Endocrinol Metab
Author:
Andreassen KV, Feigh M, Hjuler ST, Gydesen S, Henriksen JE, Beck-Nielsen H, Christiansen C, Karsdal MA, Henriksen K
Salmon calcitonin (sCT) and human calcitonin (hCT) are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(a)R) with respect to activation of cAMP signaling, β-arrestin recruitment, l...
March 18, 2014
Journal:
PLoS One
Author:
Andreassen KV, Hjuler ST, Furness SG, Sexton PM, Christopoulos A, Nosjean O, Karsdal MA, Henriksen K
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