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  1. Article ; Online: Insulin: A GOAT of medical discovery.

    Lam, Tony K T

    Cell metabolism

    2021  Volume 33, Issue 4, Page(s) 691

    MeSH term(s) Animals ; Biomedical Research/history ; Blood Glucose/analysis ; Diabetes Mellitus, Type 1/drug therapy ; Dogs ; History, 20th Century ; Humans ; Insulin/therapeutic use
    Chemical Substances Blood Glucose ; Insulin
    Language English
    Publishing date 2021-12-02
    Publishing country United States
    Document type Editorial ; Historical Article
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2021.03.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6169: Show issues Location:
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  2. Article ; Online: Obesity and the kidney: mechanistic links and therapeutic advances.

    Yau, Kevin / Kuah, Rachel / Cherney, David Z I / Lam, Tony K T

    Nature reviews. Endocrinology

    2024  

    Abstract: Obesity is strongly associated with the development of diabetes mellitus and chronic kidney disease (CKD), but there is evidence for a bidirectional relationship wherein the kidney also acts as a key regulator of body weight. In this Review, we highlight ...

    Abstract Obesity is strongly associated with the development of diabetes mellitus and chronic kidney disease (CKD), but there is evidence for a bidirectional relationship wherein the kidney also acts as a key regulator of body weight. In this Review, we highlight the mechanisms implicated in obesity-related CKD, and outline how the kidney might modulate feeding and body weight through a growth differentiation factor 15-dependent kidney-brain axis. The favourable effects of bariatric surgery on kidney function are discussed, and medical therapies designed for the treatment of diabetes mellitus that lower body weight and preserve kidney function independent of glycaemic lowering, including sodium-glucose cotransporter 2 inhibitors, incretin-based therapies and metformin, are also reviewed. In summary, we propose that kidney function and body weight are related in a bidirectional fashion, and that this interrelationship affects human health and disease.
    Language English
    Publishing date 2024-02-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2489381-X
    ISSN 1759-5037 ; 1759-5029
    ISSN (online) 1759-5037
    ISSN 1759-5029
    DOI 10.1038/s41574-024-00951-7
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    Zs.A 6336: Show issues Location:
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  3. Article ; Online: Metabolic regulation by the intestinal metformin-AMPK axis.

    Zhang, Song-Yang / Lam, Tony K T

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2851

    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Diabetes Mellitus, Type 2 ; Humans ; Hypoglycemic Agents/pharmacology ; Metformin/pharmacology
    Chemical Substances Hypoglycemic Agents ; Metformin (9100L32L2N) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2022-05-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30477-3
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  4. Article ; Online: Silencing gut CCK cells alters gut reaction to sugar.

    Yue, Jessica T Y / Duca, Frank A / Lam, Tony K T

    Nature neuroscience

    2022  Volume 25, Issue 2, Page(s) 136–138

    MeSH term(s) Brain ; Cholecystokinin/genetics ; Sugars ; Sweetening Agents
    Chemical Substances Sugars ; Sweetening Agents ; Cholecystokinin (9011-97-6)
    Language English
    Publishing date 2022-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-021-00998-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MG 67: Show issues

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  5. Article ; Online: Acute Activation of GFRAL in the Area Postrema Contributes to Glucose Regulation Independent of Weight.

    Zhang, Song-Yang / Danaei, Zahra / Bruce, Kyla / Chiu, Jennifer F M / Lam, Tony K T

    Diabetes

    2023  Volume 73, Issue 3, Page(s) 426–433

    MeSH term(s) Rats ; Animals ; Area Postrema/metabolism ; Glucose/metabolism ; Metformin/pharmacology ; Brain ; Insulins/metabolism
    Chemical Substances Glucose (IY9XDZ35W2) ; Metformin (9100L32L2N) ; Insulins
    Language English
    Publishing date 2023-12-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db23-0705
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Metabolic regulation by the intestinal metformin-AMPK axis

    Song-Yang Zhang / Tony K. T. Lam

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 3

    Abstract: AMP-activated protein kinase (AMPK) mediates the glucose-lowering effect of the antidiabetic agent metformin, but the sites of action remain unclear. In the March issue of Nature Communications, Zhang and colleagues reported that intestinal epithelium- ... ...

    Abstract AMP-activated protein kinase (AMPK) mediates the glucose-lowering effect of the antidiabetic agent metformin, but the sites of action remain unclear. In the March issue of Nature Communications, Zhang and colleagues reported that intestinal epithelium-specific AMPKα1 knockout mice fail to respond to metformin and exhibit disruption in metabolic homeostasis secondary to changes in the gut microbiome. This highlights a therapeutic potential of targeting intestinal AMPK for diabetes.
    Keywords Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Small intestinal CaSR-dependent and CaSR-independent protein sensing regulates feeding and glucose tolerance in rats.

    Li, Rosa J W / Barros, Daniel R / Kuah, Rachel / Lim, Yu-Mi / Gao, Anna / Beaudry, Jacqueline L / Zhang, Song-Yang / Lam, Tony K T

    Nature metabolism

    2024  Volume 6, Issue 1, Page(s) 39–49

    Abstract: Proteins activate small intestinal calcium sensing receptor (CaSR) and/or peptide transporter 1 (PepT1) to increase hormone ... ...

    Abstract Proteins activate small intestinal calcium sensing receptor (CaSR) and/or peptide transporter 1 (PepT1) to increase hormone secretion
    MeSH term(s) Animals ; Male ; Rats ; Caseins/metabolism ; Gastrointestinal Hormones/metabolism ; Glucose/metabolism ; Intestine, Small/metabolism ; Receptors, Calcium-Sensing/metabolism
    Chemical Substances Caseins ; Gastrointestinal Hormones ; Glucose (IY9XDZ35W2) ; Receptors, Calcium-Sensing ; extracellular calcium cation-sensing receptor, rat
    Language English
    Publishing date 2024-01-02
    Publishing country Germany
    Document type Journal Article
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-023-00942-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Bye, bye, bile: how altered bile acid composition changes small intestinal lipid sensing.

    Duca, Frank A / Lam, Tony K T

    Gut

    2020  Volume 69, Issue 9, Page(s) 1549–1550

    MeSH term(s) Animals ; Appetite Regulation ; Bile ; Bile Acids and Salts ; Intestines ; Lipids ; Mice
    Chemical Substances Bile Acids and Salts ; Lipids
    Language English
    Publishing date 2020-04-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 80128-8
    ISSN 1468-3288 ; 0017-5749
    ISSN (online) 1468-3288
    ISSN 0017-5749
    DOI 10.1136/gutjnl-2020-320873
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 160: Show issues Location:
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  9. Article ; Online: The Gut Microbiome: Connecting Diet, Glucose Homeostasis, and Disease.

    Howard, Elizabeth J / Lam, Tony K T / Duca, Frank A

    Annual review of medicine

    2021  Volume 73, Page(s) 469–481

    Abstract: Type 2 diabetes rates continue to rise unabated, underscoring the need to better understand the etiology and potential therapeutic options available for this disease. The gut microbiome plays a role in glucose homeostasis, and diabetes is associated with ...

    Abstract Type 2 diabetes rates continue to rise unabated, underscoring the need to better understand the etiology and potential therapeutic options available for this disease. The gut microbiome plays a role in glucose homeostasis, and diabetes is associated with alterations in the gut microbiome. Given that consumption of a Western diet is associated with increased metabolic disease, and that a Western diet alters the gut microbiome, it is plausible that changes in the gut microbiota mediate the dysregulation in glucose homeostasis. In this review, we highlight a few of the most significant mechanisms by which the gut microbiome can influence glucose regulation, including changes in gut permeability, gut-brain signaling, and production of bacteria-derived metabolites like short-chain fatty acids and bile acids. A better understanding of these pathways could lead to the development of novel therapeutics to target the gut microbiome in order to restore glucose homeostasis in metabolic disease.
    MeSH term(s) Diabetes Mellitus, Type 2 ; Diet ; Gastrointestinal Microbiome/physiology ; Glucose/metabolism ; Homeostasis ; Humans
    Chemical Substances Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2021-10-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 207930-6
    ISSN 1545-326X ; 0066-4219
    ISSN (online) 1545-326X
    ISSN 0066-4219
    DOI 10.1146/annurev-med-042220-012821
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ua VI Zs.321: Show issues Location:
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  10. Article ; Online: A glucose-sensing mechanism with glucose transporter 1 and pyruvate kinase in the area postrema regulates hepatic glucose production in rats.

    Li, Rosa J W / Chiu, Jennifer F M / Bruce, Kyla / Zhang, Song-Yang / Barros, Daniel R / Yue, Jessica T Y / Lam, Tony K T

    The Journal of biological chemistry

    2023  Volume 299, Issue 5, Page(s) 104633

    Abstract: The area postrema (AP) of the brain is exposed to circulating metabolites and hormones. However, whether AP detects glucose changes to exert biological responses remains unknown. Its neighboring nuclei, the nucleus tractus solitarius (NTS), responds to ... ...

    Abstract The area postrema (AP) of the brain is exposed to circulating metabolites and hormones. However, whether AP detects glucose changes to exert biological responses remains unknown. Its neighboring nuclei, the nucleus tractus solitarius (NTS), responds to acute glucose infusion by inhibiting hepatic glucose production, but the mechanism also remains elusive. Herein, we characterized AP and NTS glucose-sensing mechanisms. Infusion of glucose into the AP, like the NTS, of chow rats suppressed glucose production during the pancreatic (basal insulin)-euglycemic clamps. Glucose transporter 1 or pyruvate kinase lentiviral-mediated knockdown in the AP negated AP glucose infusion to lower glucose production, while the glucoregulatory effect of NTS glucose infusion was also negated by knocking down glucose transporter 1 or pyruvate kinase in the NTS. Furthermore, we determined that high-fat (HF) feeding disrupts glucose infusion to lower glucose production in association with a modest reduction in the expression of glucose transporter 1, but not pyruvate kinase, in the AP and NTS. However, pyruvate dehydrogenase activator dichloroacetate infusion into the AP or NTS that enhanced downstream pyruvate metabolism and recapitulated the glucoregulatory effect of glucose in chow rats still failed to lower glucose production in HF rats. We discovered that a glucose transporter 1- and pyruvate kinase-dependent glucose-sensing mechanism in the AP (as well as the NTS) lowers glucose production in chow rats and that HF disrupts the glucose-sensing mechanism that is downstream of pyruvate metabolism in the AP and NTS. These findings highlight the role of AP and NTS in mediating glucose to regulate hepatic glucose production.
    MeSH term(s) Animals ; Rats ; Area Postrema/metabolism ; Glucose/metabolism ; Glucose Transporter Type 1/genetics ; Glucose Transporter Type 1/metabolism ; Solitary Nucleus/metabolism ; Pyruvate Kinase/metabolism ; Gene Knockdown Techniques ; Lentivirus/metabolism ; Pyruvic Acid/metabolism ; Male ; Diet, High-Fat
    Chemical Substances Glucose (IY9XDZ35W2) ; Glucose Transporter Type 1 ; Pyruvate Kinase (EC 2.7.1.40) ; Pyruvic Acid (8558G7RUTR)
    Language English
    Publishing date 2023-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.104633
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    Uc I Zs.108: Show issues Location:
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