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PAN-AMPK activator ...
PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients
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- Steneberg, Pär (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Lindahl, Emma (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Dahl, Ulf (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Lidh, Emmelie (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Straseviciene, Jurate (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Backlund, Fredrik (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Kjellkvist, Elisabet (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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Berggren, Eva (author)
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Lundberg, Ingela (author)
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Bergqvist, Ingela (author)
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- Ericsson, Madelene (author)
- Umeå universitet,Fysiologisk kemi
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Eriksson, Björn (author)
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Linde, Kajsa (author)
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Westman, Jacob (author)
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- Edlund, Thomas (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Betagenon AB, Umeå, Sweden
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- Edlund, Helena, 1960- (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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(creator_code:org_t)
- 2018-06-21
- 2018
- English.
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In: JCI INSIGHT. - : American Society for Clinical Investigation. - 2379-3708. ; 3:12
- Related links:
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http://insight.jci.o...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced beta cell stress, and promoted beta cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro-and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Steneberg, Pär
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Lindahl, Emma
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Dahl, Ulf
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Lidh, Emmelie
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Straseviciene, J ...
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Backlund, Fredri ...
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show more...
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Kjellkvist, Elis ...
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Berggren, Eva
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Lundberg, Ingela
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Bergqvist, Ingel ...
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Ericsson, Madele ...
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Eriksson, Björn
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Linde, Kajsa
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Westman, Jacob
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Edlund, Thomas
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Edlund, Helena, ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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JCI INSIGHT
- By the university
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Umeå University