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  1. Article: Islet Health, Hormone Secretion, and Insulin Responsivity with Low-Carbohydrate Feeding in Diabetes.

    Locatelli, Cassandra A A / Mulvihill, Erin E

    Metabolites

    2020  Volume 10, Issue 11

    Abstract: Exploring new avenues to control daily fluctuations in glycemia has been a central theme for diabetes research since the Diabetes Control and Complications Trial (DCCT). Carbohydrate restriction has re-emerged as a means to control type 2 diabetes ... ...

    Abstract Exploring new avenues to control daily fluctuations in glycemia has been a central theme for diabetes research since the Diabetes Control and Complications Trial (DCCT). Carbohydrate restriction has re-emerged as a means to control type 2 diabetes mellitus (T2DM), becoming increasingly popular and supported by national diabetes associations in Canada, Australia, the USA, and Europe. This approval comes from many positive outcomes on HbA1c in human studies; yet mechanisms underlying their success have not been fully elucidated. In this review, we discuss the preclinical and clinical studies investigating the role of carbohydrate restriction and physiological elevations in ketone bodies directly on pancreatic islet health, islet hormone secretion, and insulin sensitivity. Included studies have clearly outlined diet compositions, including a diet with 30% or less of calories from carbohydrates.
    Language English
    Publishing date 2020-11-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo10110455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Adaptation to short-term extreme fat consumption alters intestinal lipid handling in male and female mice

    Morrow, Nadya M. / Locatelli, Cassandra A.A. / Trzaskalski, Natasha A. / Klein, Chelsea T. / Hanson, Antonio A. / Alhadi, Hadeel / Tripathi, Ishika / Clément, Andrew C. / Imran, Sara / Lorenzen-Schmidt, Ilka / Mulvihill, Erin E.

    Biochimica et biophysica acta. 2022 Nov., v. 1867, no. 11

    2022  

    Abstract: The small intestine is a highly adaptable organ serving as both a barrier to the external environment and a conduit for nutrient absorption. Enterocytes package dietary triglycerides (TG) into chylomicrons for transport into circulation; the remaining ... ...

    Abstract The small intestine is a highly adaptable organ serving as both a barrier to the external environment and a conduit for nutrient absorption. Enterocytes package dietary triglycerides (TG) into chylomicrons for transport into circulation; the remaining TGs are stored in cytosolic lipid droplets (CLDs). The current study aimed to characterize the impact of diet composition on intestinal lipid handling in male and female wild-type mice. Mice were continued on their grain-based diet (GBD) and switched to either a high-fat, high cholesterol Western-style diet (WD) or a ketogenic diet (KD) for 3 or 5 weeks. KD-fed mice displayed significantly higher plasma TG levels in response to an olive oil gavage than WD- and GBD-fed mice; TG levels were ~2-fold higher in male KD-fed mice than female KD-fed mice. Poloxamer-407 experiments revealed enhanced intestinal-TG secretion rates in male mice fed a KD upon olive oil gavage, whereas secretion rates were unchanged in female mice. Surprisingly, jejunal CLD size and TG mass after oil gavage were similar among the groups. At fasting, TG mass was significantly higher in the jejunum of male KD-fed mice and the duodenum of female KD-fed mice, providing increased substrate for chylomicron formation. In addition to greater fasting intestinal TG stores, KD-fed male mice displayed longer small intestinal lengths, while female mice displayed markedly longer jejunal villi lengths. After 5 weeks of diet, 12 h fasting-2 h refeeding experiments revealed jejunal TG levels were similar between diet groups in male mice; however, in female mice, jejunal TG mass was significantly higher in KD-fed mice compared to GBD- and WD-fed mice. These experiments reveal that KD feeding promotes distinct morphological and functional changes to the murine small intestine compared to the WD diet. Moreover, changes to intestinal lipid handling in response to carbohydrate and protein restriction manifest differently in male and female mice.
    Keywords Western diets ; carbohydrates ; cholesterol ; chylomicrons ; duodenum ; enterocytes ; fasting ; fat intake ; females ; jejunum ; ketogenic diet ; males ; nutrient uptake ; olive oil ; secretion
    Language English
    Dates of publication 2022-11
    Publishing place Elsevier B.V.
    Document type Article
    ISSN 1388-1981
    DOI 10.1016/j.bbalip.2022.159208
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Ketone ester administration improves glycemia in obese mice.

    Tabatabaei Dakhili, Seyed Amirhossein / Yang, Kunyan / Locatelli, Cassandra A A / Saed, Christina T / Greenwell, Amanda A / Chan, Jordan S F / Chahade, Jadin J / Scharff, Jared / Al-Imarah, Shahad / Eaton, Farah / Crawford, Peter A / Gopal, Keshav / Mulvihill, Erin E / Ussher, John R

    American journal of physiology. Cell physiology

    2023  Volume 325, Issue 3, Page(s) C750–C757

    Abstract: During periods of prolonged fasting/starvation, the liver generates ketones [i.e., β-hydroxybutyrate (βOHB)] that primarily serve as alternative substrates for ATP production. Previous studies have demonstrated that elevations in skeletal muscle ketone ... ...

    Abstract During periods of prolonged fasting/starvation, the liver generates ketones [i.e., β-hydroxybutyrate (βOHB)] that primarily serve as alternative substrates for ATP production. Previous studies have demonstrated that elevations in skeletal muscle ketone oxidation contribute to obesity-related hyperglycemia, whereas inhibition of succinyl CoA:3-ketoacid CoA transferase (SCOT), the rate-limiting enzyme of ketone oxidation, can alleviate obesity-related hyperglycemia. As circulating ketone levels are a key determinant of ketone oxidation rates, we tested the hypothesis that increases in circulating ketone levels would worsen glucose homeostasis secondary to increases in muscle ketone oxidation. Accordingly, male C57BL/6J mice were subjected to high-fat diet-induced obesity, whereas their lean counterparts received a standard chow diet. Lean and obese mice were orally administered either a ketone ester (KE) or placebo, followed by a glucose tolerance test. In tandem, we conducted isolated islet perifusion experiments to quantify insulin secretion in response to ketones. We observed that exogenous KE administration robustly increases circulating βOHB levels, which was associated with an improvement in glucose tolerance only in obese mice. These observations were independent of muscle ketone oxidation, as they were replicated in mice with a skeletal muscle-specific SCOT deficiency. Furthermore, the R-isomer of βOHB produced greater increases in perifusion insulin levels versus the S-isomer in isolated islets from obese mice. Taken together, acute elevations in circulating ketones promote glucose-lowering in obesity. Given that only the R-isomer of βOHB is oxidized, further studies are warranted to delineate the precise role of β-cell ketone oxidation in regulating insulin secretion.
    MeSH term(s) Animals ; Male ; Mice ; Mice, Obese ; Ketones/pharmacology ; Mice, Inbred C57BL ; Glucose/metabolism ; 3-Hydroxybutyric Acid/pharmacology ; 3-Hydroxybutyric Acid/metabolism ; Obesity/drug therapy ; Obesity/metabolism ; Hyperglycemia/drug therapy
    Chemical Substances Ketones ; Glucose (IY9XDZ35W2) ; 3-Hydroxybutyric Acid (TZP1275679)
    Language English
    Publishing date 2023-08-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00300.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.89: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Pancreas-derived DPP4 is not essential for glucose homeostasis under metabolic stress.

    Fadzeyeva, Evgenia / Locatelli, Cassandra A A / Trzaskalski, Natasha A / Nguyen, My-Anh / Capozzi, Megan E / Vulesevic, Branka / Morrow, Nadya M / Ghorbani, Peyman / Hanson, Antonio A / Lorenzen-Schmidt, Ilka / Doyle, Mary-Anne / Seymour, Richard / Varin, Elodie M / Fullerton, Morgan D / Campbell, Jonathan E / Mulvihill, Erin E

    iScience

    2023  Volume 26, Issue 5, Page(s) 106748

    Abstract: Mice systemically lacking dipeptidyl peptidase-4 (DPP4) have improved islet health, glucoregulation, and reduced obesity with high-fat diet (HFD) feeding compared to wild-type mice. Some, but not all, of this improvement can be linked to the loss of DPP4 ...

    Abstract Mice systemically lacking dipeptidyl peptidase-4 (DPP4) have improved islet health, glucoregulation, and reduced obesity with high-fat diet (HFD) feeding compared to wild-type mice. Some, but not all, of this improvement can be linked to the loss of DPP4 in endothelial cells (ECs), pointing to the contribution of non-EC types. The importance of intra-islet signaling mediated by α to β cell communication is becoming increasingly clear; thus, our objective was to determine if β cell DPP4 regulates insulin secretion and glucose tolerance in HFD-fed mice by regulating the local concentrations of insulinotropic peptides. Using β cell double incretin receptor knockout mice, β cell- and pancreas-specific
    Language English
    Publishing date 2023-04-26
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106748
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Adaptation to short-term extreme fat consumption alters intestinal lipid handling in male and female mice.

    Morrow, Nadya M / Locatelli, Cassandra A A / Trzaskalski, Natasha A / Klein, Chelsea T / Hanson, Antonio A / Alhadi, Hadeel / Tripathi, Ishika / Clément, Andrew C / Imran, Sara / Lorenzen-Schmidt, Ilka / Mulvihill, Erin E

    Biochimica et biophysica acta. Molecular and cell biology of lipids

    2022  Volume 1867, Issue 11, Page(s) 159208

    Abstract: The small intestine is a highly adaptable organ serving as both a barrier to the external environment and a conduit for nutrient absorption. Enterocytes package dietary triglycerides (TG) into chylomicrons for transport into circulation; the remaining ... ...

    Abstract The small intestine is a highly adaptable organ serving as both a barrier to the external environment and a conduit for nutrient absorption. Enterocytes package dietary triglycerides (TG) into chylomicrons for transport into circulation; the remaining TGs are stored in cytosolic lipid droplets (CLDs). The current study aimed to characterize the impact of diet composition on intestinal lipid handling in male and female wild-type mice. Mice were continued on their grain-based diet (GBD) and switched to either a high-fat, high cholesterol Western-style diet (WD) or a ketogenic diet (KD) for 3 or 5 weeks. KD-fed mice displayed significantly higher plasma TG levels in response to an olive oil gavage than WD- and GBD-fed mice; TG levels were ~2-fold higher in male KD-fed mice than female KD-fed mice. Poloxamer-407 experiments revealed enhanced intestinal-TG secretion rates in male mice fed a KD upon olive oil gavage, whereas secretion rates were unchanged in female mice. Surprisingly, jejunal CLD size and TG mass after oil gavage were similar among the groups. At fasting, TG mass was significantly higher in the jejunum of male KD-fed mice and the duodenum of female KD-fed mice, providing increased substrate for chylomicron formation. In addition to greater fasting intestinal TG stores, KD-fed male mice displayed longer small intestinal lengths, while female mice displayed markedly longer jejunal villi lengths. After 5 weeks of diet, 12 h fasting-2 h refeeding experiments revealed jejunal TG levels were similar between diet groups in male mice; however, in female mice, jejunal TG mass was significantly higher in KD-fed mice compared to GBD- and WD-fed mice. These experiments reveal that KD feeding promotes distinct morphological and functional changes to the murine small intestine compared to the WD diet. Moreover, changes to intestinal lipid handling in response to carbohydrate and protein restriction manifest differently in male and female mice.
    MeSH term(s) Animals ; Chylomicrons/metabolism ; Diet, High-Fat ; Enterocytes/metabolism ; Female ; Male ; Mice ; Olive Oil/metabolism ; Triglycerides/metabolism
    Chemical Substances Chylomicrons ; Olive Oil ; Triglycerides
    Language English
    Publishing date 2022-08-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 60-7
    ISSN 1879-2618 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2618 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbalip.2022.159208
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.247: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  6. Article ; Online: Recent Developments in Islet Biology: A Review With Patient Perspectives.

    Basu, Lahari / Bhagat, Vriti / Ching, Ma Enrica Angela / Di Giandomenico, Anna / Dostie, Sylvie / Greenberg, Dana / Greenberg, Marley / Hahm, Jiwon / Hilton, N Zoe / Lamb, Krista / Jentz, Emelien M / Larsen, Matt / Locatelli, Cassandra A A / Maloney, MaryAnn / MacGibbon, Christine / Mersali, Farida / Mulchandani, Christina Marie / Najam, Adhiyat / Singh, Ishnoor /
    Weisz, Tom / Wong, Jordan / Senior, Peter A / Estall, Jennifer L / Mulvihill, Erin E / Screaton, Robert A

    Canadian journal of diabetes

    2022  Volume 47, Issue 2, Page(s) 207–221

    Abstract: Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more than 2,000 peer-reviewed articles on islet biology were published in 2021. Herein, we ... ...

    Abstract Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more than 2,000 peer-reviewed articles on islet biology were published in 2021. Herein, we highlight noteworthy advances in islet research between January 2021 and April 2022, focussing on 5 areas. First, we discuss new insights into the role of glucokinase, mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase and mitochondrial function on insulin secretion from the pancreatic β cell, provided by new genetically modified mouse models and live imaging. We then discuss a new connection between lipid handling and improved insulin secretion in the context of glucotoxicity, focussing on fatty acid-binding protein 4 and fetuin-A. Advances in high-throughput "omic" analysis evolved to where one can generate more finely tuned genetic and molecular profiles within broad classifications of type 1 diabetes and type 2 diabetes. Next, we highlight breakthroughs in diabetes treatment using stem cell-derived β cells and innovative strategies to improve islet survival posttransplantation. Last, we update our understanding of the impact of severe acute respiratory syndrome-coronavirus-2 infection on pancreatic islet function and discuss current evidence regarding proposed links between COVID and new-onset diabetes. We address these breakthroughs in 2 settings: one for a scientific audience and the other for the public, particularly those living with or affected by diabetes. Bridging biomedical research in diabetes to the community living with or affected by diabetes, our partners living with type 1 diabetes or type 2 diabetes also provide their perspectives on these latest advances in islet biology.
    MeSH term(s) Animals ; Mice ; Biology ; COVID-19 ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 2 ; Insulin/metabolism ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/metabolism ; Humans
    Chemical Substances Insulin
    Language English
    Publishing date 2022-11-08
    Publishing country Canada
    Document type Journal Article ; Review
    ISSN 2352-3840
    ISSN (online) 2352-3840
    DOI 10.1016/j.jcjd.2022.11.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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