Endocrinology, Obesity
4. May 2020
Dose Frequency Optimization of the Dual Amylin and Calcitonin Receptor Agonist KBP-088: Long-Lasting Improvement in Food Preference and Body Weight Loss
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…
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Endocrinology, Obesity, Type 2-Diabetes, Hepatic System
21. Apr 2020
The Calcitonin Receptor Plays a Major Role in Glucose Regulation as a Function of Dual Amylin and Calcitonin Receptor Agonist Therapy
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 …
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Endocrinology, Obesity, Hepatic System
14. Apr 2020
The Dual Amylin and Calcitonin Receptor Agonist, KBP-066, Induces an Equally Potent Weight Loss Across a Broad Dose Range While Higher Doses May Further Improve Insulin Action
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…
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Journal:
Authors:
- Sonne N,
- Larsen AT,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Obesity, Endocrinology
1. Jul 2019
The Dual Amylin and Calcitonin Receptor Agonist KBP-088 Induces Weight Loss and Improves Insulin Sensitivity Superior to Chronic Amylin Therapy
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 …
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Gehring K,
- Karsdal MA,
- Henriksen K,
Bone, Rheumatology, Osteoarthritis
5. Jun 2019
A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model
OBJECTIVES:
Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor a…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Lövfall H,
- Karsdal MA,
- Andreassen KV,
- Thudium CS,
- Henriksen K,
Rheumatology, Rheumatoid Arthritis, Bone
22. Feb 2019
Combining Naproxen and a Dual Amylin and Calcitonin Receptor Agonist improves pain and structural outcomes in the Collagen-Induced Arthritis rat model
BACKGROUND:
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction w…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Löfvall H,
- Ding M,
- Karsdal MA,
- Andreassen KV,
- Schneider Thudium C,
- Henriksen K,
Type 2-Diabetes, Obesity, Endocrinology
24. Apr 2017
The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Works as Adjunct to Metformin on Fasting Hyperglycemia and HbA1c in a Rat Model of Type 2 Diabetes
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…
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Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Obesity
14. Mar 2017
Optimization of Tolerability and Efficacy of Dual Amylin and Calcitonin Receptor Agonist, KBP-089, through Dose Escalation and Combination with a GLP-1 Analogue
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 KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in HFD rats. KBP-089 …
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Journal:
Authors:
- Gydesen S,
- Andreassen KV,
- Hjuler ST,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Type 2-Diabetes
21. Jan 2017
A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference
BACKGROUND AND PURPOSE:
Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities.
EXPERIMENTAL APPROACH:
The…
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Journal:
Authors:
- Gydesen S,
- Hjuler ST,
- Freving Z,
- Andreassen KV,
- Sonne N,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
1. Aug 2016
The dual amylin- and calcitonin-receptor agonist KBP-042 increases insulin sensitivity and induces weight loss in rats with obesity
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…
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Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Pedersen SL,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
1. May 2016
KBP-088, a novel DACRA with prolonged receptor activation, is superior to davalintide in terms of efficacy on body weight
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…
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Journal:
Authors:
- Gydesen S,
- Hjuler ST,
- Christensen JM,
- Karsdal MA,
- Arbit E,
- Andreassen KV,
Endocrinology, Type 2-Diabetes
5. Sep 2015
KBP-042 improves bodyweight and glucose homeostasis with indices of increased insulin sensitivity irrespective of route of administration
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…
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Journal:
Authors:
- Hjuler ST,
- Andreassen KV,
- Gydesen S,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
14. Aug 2014
Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats
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…
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Journal:
Authors:
- Feigh M,
- Hjuler ST,
- Andreassen KV,
- Gydesen S,
- Ottosen I,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
31. Jul 2014
A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats
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…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Type 2-Diabetes, Obesity, Endocrinology
6. May 2014
A Novel Oral Dual Amylin and Calcitonin Receptor Agonist (KBP-042) Exerts Anti-Obesity and Anti-Diabetic Effects in Rats
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…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
18. Mar 2014
Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias
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…
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Journal:
Authors:
- Andreassen KV,
- Hjuler ST,
- Furness SG,
- Sexton PM,
- Christopoulos A,
- Nosjean O,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
14. Feb 2013
Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model
Articular cartilage deterioration, which includes cartilage degradation and chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD). Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a robust explants model for investigation of hypertrophy should incl…
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Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Endocrinology, Type 2-Diabetes
4. Feb 2013
Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats
OBJECTIVE:
Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Hjuler ST,
- Nielsen RH,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Endocrinology, Type 1-Diabetes
10. Oct 2012
Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: how markers of β-cell loss may assist
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 …
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Andreassen KV,
- Hjuler ST,
- Feigh M,
- Bay-Jensen AC,
- Zheng Q,
- Henriksen K,
- Karsdal MA,
Endocrinology, Type 2-Diabetes
16. Sep 2012
Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats
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 …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Neutzsky-Wulff AV,
- Petersen ST,
- Hansen C,
- Bay-Jensen AC,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Bone
16. Sep 2012
A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts
Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was c…
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Journal:
Authors:
- Henriksen K,
- Andreassen KV,
- Thudium CS,
- Gudmann KN,
- Moscatelli I,
- Crüger-Hansen CE,
- Schulz AS,
- Dziegiel MH,
- Richter J,
- Karsdal MA,
- Neutzsky-Wulff AV,
Rheumatology, Osteoarthritis
1. Jul 2012
The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage
OBJECTIVE:
Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. W…
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Journal:
Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Bone, Osteoporosis
11. Dec 2011
Glucocorticoids exert context-dependent effects on cells of the joint in vitro
INTRODUCTION:
Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthri…
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Journal:
Authors:
- Madsen SH,
- Andreassen KV,
- Christensen ST,
- Karsdal MA,
- Sverdrup FM,
- Bay-Jensen AC,
- Henriksen K,
Endocrinology, Type 2-Diabetes
13. Oct 2011
A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats
AIM:
To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes.…
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Journal:
Authors:
- Feigh M,
- Henriksen K,
- Andreassen KV,
- Hansen C,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,