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Keywords: type 2 diabetes
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Articles

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator

Ashley J. Ovens, Yi Sing Gee, Naomi X.Y. Ling, Dingyi Yu, Justin P. Hardee, Jin D. Chung, Kevin R.W. Ngoei, Nicholas J. Waters, Nolan J. Hoffman, John W. Scott, Kim Loh, Katrin Spengler, Regine Heller, Michael W. Parker, Gordon S. Lynch, Fei Huang, Sandra Galic, Bruce E. Kemp, Jonathan B. Baell, Jonathan S. Oakhill, Christopher G. Langendorf
Journal: Biochemical Journal
Biochem J (2022) 479 (11): 1181–1204.
https://doi.org/10.1042/BCJ20220067
Published: 08 June 2022
... strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2β2γ1 isoform combination as the heterotrimer complex primarily responsible. With the goal of developing α2β2-specific activators, here we perform structure/function analysis of the 2...
View articletitled, Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator
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Includes: Supplementary data
Articles

A nexus of miR-1271, PAX4 and ALK/RYK influences the cytoskeletal architectures in Alzheimer's Disease and Type 2 Diabetes

Piyali Majumder, Kaushik Chanda, Debajyoti Das, Brijesh Kumar Singh, Partha Chakrabarti, Nihar Ranjan Jana, Debashis Mukhopadhyay
Journal: Biochemical Journal
Biochem J (2021) 478 (17): 3297–3317.
https://doi.org/10.1042/BCJ20210175
Published: 14 September 2021
...Piyali Majumder; Kaushik Chanda; Debajyoti Das; Brijesh Kumar Singh; Partha Chakrabarti; Nihar Ranjan Jana; Debashis Mukhopadhyay Alzheimer's Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Reportedly, two non-canonical Receptor Tyrosine Kinases (RTKs), ALK...
View articletitled, A nexus of miR-1271, PAX4 and ALK/RYK influences the cytoskeletal architectures in Alzheimer's Disease and Type 2 Diabetes
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Includes: Supplementary data
Articles

Impact of pesticide exposure on adipose tissue development and function

In Collection
Adipose biology
Robert M. Gutgesell, Evangelia E. Tsakiridis, Shanza Jamshed, Gregory R. Steinberg, Alison C. Holloway
Journal: Biochemical Journal
Biochem J (2020) 477 (14): 2639–2653.
https://doi.org/10.1042/BCJ20200324
Published: 29 July 2020
... and metabolic diseases such as type 2 diabetes. In this review, we discuss epidemiological evidence linking pesticide exposure with body mass index (BMI) and the incidence of diabetes. We then review preclinical studies in rodent models which have directly evaluated the effects of different classes...
View articletitled, Impact of pesticide exposure on adipose tissue development and function
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Articles

The NLRP3 inflammasome regulates adipose tissue metabolism

In Collection
Adipose biology
Nicole G. Barra, Brandyn D. Henriksbo, Fernando F. Anhê, Jonathan D. Schertzer
Journal: Biochemical Journal
Biochem J (2020) 477 (6): 1089–1107.
https://doi.org/10.1042/BCJ20190472
Published: 23 March 2020
... Society 2020 adipocytes immunometabolism inflammasome inflammation obesity type 2 diabetes Adipose tissue is a critical energy storage site, where lipids are primarily stored as triglycerides in adipocytes. White adipocytes mainly act as a lipid storage and release site. In a state...
View articletitled, The NLRP3 inflammasome regulates adipose tissue metabolism
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Articles

α-catenin isoforms are regulated by glucose and involved in regulating insulin secretion in rat clonal β-cell models

Waruni C. Dissanayake, Brie Sorrenson, Kate L. Lee, Sandra Barre, Peter R. Shepherd
Journal: Biochemical Journal
Biochem J (2020) 477 (4): 763–772.
https://doi.org/10.1042/BCJ20190832
Published: 20 February 2020
... and the Biochemical Society under a transformative agreement with CAUL. actin alpha-catenin beta-catenin calcium influx insulin secretion type 2 diabetes The proper control of glucose homeostasis relies on the appropriate levels of insulin being secreted from the β-cells in the pancreas so...
View articletitled, α-catenin isoforms are regulated by glucose and involved in regulating insulin secretion in rat clonal β-cell models
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Articles

Insulin and β-adrenergic receptors mediate lipolytic and anti-lipolytic signalling that is not altered by type 2 diabetes in human adipocytes

In Collection
Editors' pick of research highlights published in the Biochemical Journal in 2018 & 2019
Cecilia Jönsson, Ana P. Castor Batista, Preben Kjølhede, Peter Strålfors
Journal: Biochemical Journal
Biochem J (2019) 476 (19): 2883–2908.
https://doi.org/10.1042/BCJ20190594
Published: 11 October 2019
...Cecilia Jönsson; Ana P. Castor Batista; Preben Kjølhede; Peter Strålfors Control of fatty acid storage and release in adipose tissue is fundamental in energy homeostasis and the development of obesity and type 2 diabetes. We here take the whole signalling network into account to identify how...
View articletitled, Insulin and β-adrenergic receptors mediate lipolytic and anti-lipolytic signalling that is not altered by type 2 diabetes in human adipocytes
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Includes: Supplementary data
Articles

Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

Connie Hung, Casey Bronec, Eleonora Napoli, James Graham, Kimber L. Stanhope, Ilaria Marsilio, Maria Cecilia Giron, Peter J. Havel, Cecilia Giulivi
Journal: Biochemical Journal
Biochem J (2018) 475 (3): 649–662.
https://doi.org/10.1042/BCJ20170899
Published: 14 February 2018
...Connie Hung; Casey Bronec; Eleonora Napoli; James Graham; Kimber L. Stanhope; Ilaria Marsilio; Maria Cecilia Giron; Peter J. Havel; Cecilia Giulivi Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding...
View articletitled, Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes
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Includes: Supplementary data
Articles

Recombinant human islet amyloid polypeptide forms shorter fibrils and mediates β-cell apoptosis via generation of oxidative stress

Richa Dubey, Pooja Minj, Nikita Malik, Devika M. Sardesai, Shruti H. Kulkarni, Jhankar D. Acharya, Neel Sarovar Bhavesh, Shilpy Sharma, Ashutosh Kumar
Journal: Biochemical Journal
Biochem J (2017) 474 (23): 3915–3934.
https://doi.org/10.1042/BCJ20170323
Published: 16 November 2017
...Richa Dubey; Pooja Minj; Nikita Malik; Devika M. Sardesai; Shruti H. Kulkarni; Jhankar D. Acharya; Neel Sarovar Bhavesh; Shilpy Sharma; Ashutosh Kumar Protein misfolding and aggregation play an important role in many human diseases including Alzheimer's, Parkinson's and type 2 diabetes mellitus...
View articletitled, Recombinant human islet amyloid polypeptide forms shorter fibrils and mediates β-cell apoptosis via generation of oxidative stress
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Includes: Supplementary data
Articles

Niclosamide blocks glucagon phosphorylation of Ser 552 on β-catenin in primary rat hepatocytes via PKA signalling

Md. Kamrul H. Chowdhury, Lindsay E. Wu, James L.J. Coleman, Nicola J. Smith, Margaret J. Morris, Peter R. Shepherd, Greg C. Smith
Journal: Biochemical Journal
Biochem J (2016) 473 (9): 1247–1255.
https://doi.org/10.1042/BCJ20160121
Published: 26 April 2016
... glucagon signalling that leads to increased β-catenin activity that can be reversed with the antihelminthic drug niclosamide, which has recently shown promise as a potential treatment of T2D (Type 2 diabetes). This novel finding could be useful in liver cancer treatment, particularly in the context of T2D...
View articletitled, Niclosamide blocks glucagon phosphorylation of Ser 552 on β-catenin in primary rat hepatocytes via PKA signalling
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Articles

Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets

Jonathan Barlow, Verena Hirschberg Jensen, Martin Jastroch, Charles Affourtit
Journal: Biochemical Journal
Biochem J (2016) 473 (4): 487–496.
https://doi.org/10.1042/BJ20151080
Published: 09 February 2016
... pancreatic β-cells Type 2 diabetes Type 2 diabetes affects over 500 million people worldwide [ 1 ] and it is generally accepted that obesity is a major risk factor in the development of this metabolic disease [ 2 ]. The obese state is characterized by high non-esterified fatty acids (NEFA) levels...
View articletitled, Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets
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Articles

miRNA let-7 expression is regulated by glucose and TNF-α by a remote upstream promoter

Mutsumi Katayama, Rasmus J.O. Sjögren, Brendan Egan, Anna Krook
Journal: Biochemical Journal
Biochem J (2015) 472 (2): 147–156.
https://doi.org/10.1042/BJ20150224
Published: 13 November 2015
...Mutsumi Katayama; Rasmus J.O. Sjögren; Brendan Egan; Anna Krook miRNAs regulate protein abundance and control diverse aspects of cellular processes and biological functions in metabolic diseases, such as obesity and type 2 diabetes (T2D). Let (lethal)-7 miRNAs specifically targets genes associated...
View articletitled, miRNA let-7 expression is regulated by glucose and TNF-α by a remote upstream promoter
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Articles

Repurposing metformin: an old drug with new tricks in its binding pockets

Rosina Pryor, Filipe Cabreiro
Journal: Biochemical Journal
Biochem J (2015) 471 (3): 307–322.
https://doi.org/10.1042/BJ20150497
Published: 16 October 2015
... the diseases of old age, including type 2 diabetes (T2D), cardiovascular disease (CVD) and cancer. Developing new ways to improve health in the elderly is therefore a top priority for biomedical research. Although our understanding of the molecular basis of these morbidities has advanced rapidly, effective...
View articletitled, Repurposing metformin: an old drug with new tricks in its binding pockets
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Articles

Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity

Rebecca J. Ford, Morgan D. Fullerton, Stephen L. Pinkosky, Emily A. Day, John W. Scott, Jonathan S. Oakhill, Adam L. Bujak, Brennan K. Smith, Justin D. Crane, Regje M. Blümer, Katarina Marcinko, Bruce E. Kemp, Hertzel C. Gerstein, Gregory R. Steinberg
Journal: Biochemical Journal
Biochem J (2015) 468 (1): 125–132.
https://doi.org/10.1042/BJ20150125
Published: 05 May 2015
... diabetes Non-alcoholic fatty liver disease (NAFLD) is estimated to affect nearly 40% of all adults and more than 80% of those with type 2 diabetes (T2D) [ 1 ]. Elevated rates of liver fatty acid synthesis ( de novo lipogenesis) cause NAFLD in humans [ 2 ] and NAFLD may promote the development...
View articletitled, Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity
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Articles

Novel insights into pancreatic β-cell glucolipotoxicity from real-time functional analysis of mitochondrial energy metabolism in INS-1E insulinoma cells

Jonathan Barlow, Charles Affourtit
Journal: Biochemical Journal
Biochem J (2013) 456 (3): 417–426.
https://doi.org/10.1042/BJ20131002
Published: 22 November 2013
... Obesity-related pancreatic β-cell failure contributes to development of Type 2 diabetes. We show that defects in mitochondrial oxidative phosphorylation largely account for fatty-acid-induced impairment of glucose-stimulated insulin secretion, but not for the lipotoxicity-related loss of β-cell viability...
View articletitled, Novel insights into pancreatic β-cell glucolipotoxicity from real-time functional analysis of mitochondrial energy metabolism in INS-1E insulinoma cells
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Articles

Time-resolved metabolomics analysis of β-cells implicates the pentose phosphate pathway in the control of insulin release

Peter Spégel, Vladimir V. Sharoyko, Isabel Goehring, Anders P. H. Danielsson, Siri Malmgren, Cecilia L. F. Nagorny, Lotta E. Andersson, Thomas Koeck, Geoffrey W. G. Sharp, Susanne G. Straub, Claes B. Wollheim, Hindrik Mulder
Journal: Biochemical Journal
Biochem J (2013) 450 (3): 595–605.
https://doi.org/10.1042/BJ20121349
Published: 28 February 2013
... Biochemical Society 2013 glutathione islets mass spectrometry NADPH ribose 5-phosphate Type 2 diabetes A metabolomics approach allows a deeper understanding of metabolism. The goal of metabolomics is an unbiased and global determination of all metabolites in a biological sample [ 16...
View articletitled, Time-resolved metabolomics analysis of β-cells implicates the pentose phosphate pathway in the control of insulin release
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Includes: Supplementary data
Articles

The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a

Amy R. Cameron, Katherine Wallace, Lisa Logie, Alan R. Prescott, Terry G. Unterman, Jean Harthill, Graham Rena
Journal: Biochemical Journal
Biochem J (2012) 443 (1): 57–64.
https://doi.org/10.1042/BJ20112124
Published: 14 March 2012
...Amy R. Cameron; Katherine Wallace; Lisa Logie; Alan R. Prescott; Terry G. Unterman; Jean Harthill; Graham Rena Many diseases of aging including AD (Alzheimer's disease) and T2D (Type 2 diabetes) are strongly associated with common risk factors, suggesting that there may be shared aging mechanisms...
View articletitled, The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a
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Articles

Ceramide synthase 4 and de novo production of ceramides with specific N-acyl chain lengths are involved in glucolipotoxicity-induced apoptosis of INS-1 β-cells

Julien Véret, Nicolas Coant, Evgeny V. Berdyshev, Anastasia Skobeleva, Nicole Therville, Danielle Bailbé, Irina Gorshkova, Viswanathan Natarajan, Bernard Portha, Hervé Le Stunff
Journal: Biochemical Journal
Biochem J (2011) 438 (1): 177–189.
https://doi.org/10.1042/BJ20101386
Published: 27 July 2011
...) was added to lipid extracts which were incubated for 30 min at 210 °C. After cooling, water and 4.2% ammonium molybdate in 4 M HCl/0.045% Malachite Green (1:3, v/v) was added. Samples were incubated at 37 °C for 30 min, and absorbance was measured at 660 nm. Type 2 diabetes mellitus is a disease...
View articletitled, Ceramide synthase 4 and de novo production of ceramides with specific N-acyl chain lengths are involved in glucolipotoxicity-induced apoptosis of INS-1 β-cells
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Includes: Supplementary data
Articles

A lipidomic screen of palmitate-treated MIN6 β-cells links sphingolipid metabolites with endoplasmic reticulum (ER) stress and impaired protein trafficking

Ebru Boslem, Gemma MacIntosh, Amanda M. Preston, Clarissa Bartley, Anna K. Busch, Maria Fuller, D. Ross Laybutt, Peter J. Meikle, Trevor J. Biden
Journal: Biochemical Journal
Biochem J (2011) 435 (1): 267–276.
https://doi.org/10.1042/BJ20101867
Published: 15 March 2011
...Ebru Boslem; Gemma MacIntosh; Amanda M. Preston; Clarissa Bartley; Anna K. Busch; Maria Fuller; D. Ross Laybutt; Peter J. Meikle; Trevor J. Biden Saturated fatty acids promote lipotoxic ER (endoplasmic reticulum) stress in pancreatic β-cells in association with Type 2 diabetes. To address...
View articletitled, A lipidomic screen of palmitate-treated MIN6 β-cells links sphingolipid metabolites with endoplasmic reticulum (ER) stress and impaired protein trafficking
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Includes: Supplementary data
Articles

NF-κB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance

Suman Dasgupta, Sushmita Bhattacharya, Anindita Biswas, Subeer S. Majumdar, Satinath Mukhopadhyay, Sukanta Ray, Samir Bhattacharya
Journal: Biochemical Journal
Biochem J (2010) 429 (3): 451–462.
https://doi.org/10.1042/BJ20100330
Published: 14 July 2010
...Suman Dasgupta; Sushmita Bhattacharya; Anindita Biswas; Subeer S. Majumdar; Satinath Mukhopadhyay; Sukanta Ray; Samir Bhattacharya Fetuin-A, a hepatic secretory protein, has recently been implicated in insulin resistance and Type 2 diabetes. It is an endogenous inhibitor of insulin receptor...
View articletitled, NF-κB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance
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Includes: Supplementary data
Articles

Mechanisms involved in the developmental programming of adulthood disease

Matthew J. Warner, Susan E. Ozanne
Journal: Biochemical Journal
Biochem J (2010) 427 (3): 333–347.
https://doi.org/10.1042/BJ20091861
Published: 14 April 2010
... structures and the epigenome, and (ii) how aberrant mitochondrial function can potentially lead to the development of Type 2 diabetes and other features of metabolic syndrome. 1 To whom correspondence should be addressed (email [email protected] ). 22 12 2009 18 2 2010 19 2 2010...
View articletitled, Mechanisms involved in the developmental programming of adulthood disease
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Articles

Brd2 disruption in mice causes severe obesity without Type 2 diabetes

Fangnian Wang, Hongsheng Liu, Wanda P. Blanton, Anna Belkina, Nathan K. Lebrasseur, Gerald V. Denis
Journal: Biochemical Journal
Biochem J (2010) 425 (1): 71–85.
https://doi.org/10.1042/BJ20090928
Published: 14 December 2009
... in Type 2 diabetes. Current searches for relevant genes consume significant effort. We have reported previously a novel double bromodomain protein called Brd2, which is a transcriptional co-activator/co-repressor with SWI/SNF (switch mating type/sucrose non-fermenting)-like functions that regulates...
View articletitled, Brd2 disruption in mice causes severe obesity without Type 2 diabetes
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Includes: Supplementary data
Articles

Pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) deficiency attenuates the long-term negative effects of a high-saturated fat diet

Byounghoon Hwang, Nam Ho Jeoung, Robert A. Harris
Journal: Biochemical Journal
Biochem J (2009) 423 (2): 243–252.
https://doi.org/10.1042/BJ20090390
Published: 25 September 2009
...Byounghoon Hwang; Nam Ho Jeoung; Robert A. Harris The hypothesis that PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) has potential as a target for the treatment of type 2 diabetes was tested by feeding wild-type and PDHK4 knockout mice a high saturated fat diet that induces hyperglycemia...
View articletitled, Pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) deficiency attenuates the long-term negative effects of a high-saturated fat diet
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Articles

Regulation and function of triacylglycerol lipases in cellular metabolism

Matthew J. Watt, Gregory R. Steinberg
Journal: Biochemical Journal
Biochem J (2008) 414 (3): 313–325.
https://doi.org/10.1042/BJ20080305
Published: 27 August 2008
... lipase (HSL) obesity skeletal muscle Type 2 diabetes Intracellular lipid pools are in a constant state of flux, with overall lipid content ultimately dependent on the balance between the rates of FA (fatty acid) uptake, esterification, hydrolysis and oxidation [ 1 – 3 ]. FAs are used...
View articletitled, Regulation and function of triacylglycerol lipases in cellular metabolism
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Includes: Multimedia, Supplementary data
Articles

Inhibition of the interaction between protein phosphatase 1 glycogen-targeting subunit and glycogen phosphorylase increases glycogen synthesis in primary rat hepatocytes

Darya Zibrova, Rolf Grempler, Rüdiger Streicher, Stefan G. Kauschke
Journal: Biochemical Journal
Biochem J (2008) 412 (2): 359–366.
https://doi.org/10.1042/BJ20071483
Published: 14 May 2008
...Darya Zibrova; Rolf Grempler; Rüdiger Streicher; Stefan G. Kauschke In Type 2 diabetes, increased glycogenolysis contributes to the hyperglycaemic state, therefore the inhibition of GP (glycogen phosphorylase), a key glycogenolytic enzyme, is one of the possibilities to lower plasma glucose levels...
View articletitled, Inhibition of the interaction between protein phosphatase 1 glycogen-targeting subunit and glycogen phosphorylase increases glycogen synthesis in primary rat hepatocytes
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Articles

Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion

Charles Affourtit, Martin D. Brand
Journal: Biochemical Journal
Biochem J (2008) 409 (1): 199–204.
https://doi.org/10.1042/BJ20070954
Published: 11 December 2007
... secretion mitochondrial uncoupling oxidative phosphorylation pancreatic β-cell Type 2 diabetes uncoupling protein-2 (UCP2) Type 2 diabetes is rapidly becoming a global pandemic. Although the development of this metabolic disorder is understood incompletely, it is evident that pancreatic β-cell...
View articletitled, Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion
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Articles

Stronger control of ATP/ADP by proton leak in pancreatic β-cells than skeletal muscle mitochondria

Charles Affourtit, Martin D. Brand
Journal: Biochemical Journal
Biochem J (2006) 393 (1): 151–159.
https://doi.org/10.1042/BJ20051280
Published: 12 December 2005
... be addressed (email [email protected] ). 5 8 2005 26 8 2005 2 9 2005 2 9 2005 The Biochemical Society, London 2006 metabolic control analysis mitochondrial oxidative phosphorylation modular kinetics pancreatic beta cell (β-cell) proton leak type 2 diabetes...
View articletitled, Stronger control of ATP/ADP by proton leak in pancreatic β-cells than skeletal muscle mitochondria
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Articles

Pancreatic beta-cell granule peptides form heteromolecular complexes which inhibit islet amyloid polypeptide fibril formation

Emma T. A. S. JAIKARAN, Melanie R. NILSSON, Anne CLARK
Journal: Biochemical Journal
Biochem J (2004) 377 (3): 709–716.
https://doi.org/10.1042/bj20030852
Published: 01 February 2004
...Emma T. A. S. JAIKARAN; Melanie R. NILSSON; Anne CLARK Islet amyloid polypeptide (IAPP), or ‘amylin’, is co-stored with insulin in secretory granules of pancreatic islet β-cells. In Type 2 diabetes, IAPP converts into a β-sheet conformation and oligomerizes to form amyloid fibrils and islet...
View articletitled, Pancreatic beta-cell granule peptides form heteromolecular complexes which inhibit islet amyloid polypeptide fibril formation
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