Skip to main content
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Section 1: Insulin Release: Some Molecular Requisites

Two-Photon Excitation Imaging of Pancreatic Islets With Various Fluorescent Probes

  1. Noriko Takahashi124,
  2. Tomomi Nemoto124,
  3. Ryoichi Kimura124,
  4. Akira Tachikawa24,
  5. Akiko Miwa35,
  6. Haruo Okado35,
  7. Yasushi Miyashita2,
  8. Masamitsu Iino24,
  9. Takashi Kadowaki2 and
  10. Haruo Kasai14
  1. 1Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Japan
  2. 2University of Tokyo, School of Medicine, Bunkyo-ku, Tokyo, Japan
  3. 3Department of Molecular Physiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan
  4. 4Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Hongo, Bunkyo-ku, Japan
  5. 5CREST of JST, Kawaguchi, Saitama, Japan
    Diabetes 2002 Feb; 51(suppl 1): S25-S28. https://doi.org/10.2337/diabetes.51.2007.S25
    PreviousNext
    • Article
    • Figures & Tables
    • Info & Metrics
    • PDF
    Loading

    Abstract

    Various fluorescent probes were assessed for investigating intact islets of Langerhans using two-photon excitation imaging. Polar fluorescent tracers applied on the outside rapidly (within 3 min) penetrated deep into the islets via microvessels. Likewise, an adenovirus carrying a Ca2+-sensitive green fluorescent protein mutant gene, yellow cameleon 2.1, was successfully transfected and enabled ratiometric cytosolic Ca2+ measurement of cells in the deep layers of the islets. Interestingly, FM1-43, which is lipophilic and does not permeate the plasma membrane, also rapidly reached deep cell layers of the islets. In contrast, lipophilic fluorescent probes that permeate the plasma membrane (for example, fura-2-acetoxymethyl and BODIPY-forskolin) accumulated in the superficial cell layers of the islets, even 30 min after application. Thus, two-photon excitation imaging of pancreatic islets is a promising method for clarifying signaling mechanisms of islet cells, particularly when it is combined with membrane-impermeable probes. In addition, our data suggest that membrane-permeable antagonists may affect only the superficial cell layers of islets, and so their negative effects should be interpreted with caution.

    The two-photon excitation microscope uses a near-infrared ultrashort-pulse laser for the excitation of fluorescent probes rather than the visible continuous laser used in the confocal microscope (1). Because two-photon excitation only occurs at the focal plane of the objective lens (1), tomographic images can be obtained without the use of a confocal pinhole in front of the photodetector. This imaging technique is particularly suited for investigating living tissue preparations. First, phototoxic effects are markedly reduced because the excitation occurs only at the focal plane. Second, the effects of light scattering are minimized by the use of near-infrared light for excitation and by the absence of confocal pinhole for photodetection. In fact, two-photon excitation imaging has been applied to various neuronal preparations (1–3) and exocrine tissue (4) and has proven to be a promising method for the analysis of cellular mechanisms in intact tissues, which preserve their original structures. Such imaging has also been conducted in pancreatic islets, but only with autofluorescence (5,6).

    Here, we have assessed various fluorescent indicators for investigating intact islets of Langerhans using two-photon excitation imaging. We have found that hydrophilic probes are particularly useful because they readily penetrate into the deep cell layers of islets via microvessels. In contrast, membrane-permeable substances tend to accumulate in the superficial cell layers.

    RESEARCH DESIGN AND METHODS

    Preparation of mouse pancreatic islets.

    Pancreatic islets were isolated from ICR mice aged >8 weeks using collagenase and cultured for between 1 h and 3 days (7). The islets cultured for 1 day were immersed in a solution (solution A) containing 140 mmol/l NaCl, 5 mmol/l KCl, 2 mmol/l CaCl2, 1 mmol/l MgCl2, 10 mmol/l Hepes-NaOH (pH 7.3), and 2 mmol/l glucose. The solution also contained lucifer yellow (0.4 mmol/l), sulforhodamine B (0.7 mmol/l), FM1-43 (4 μmol/l), BODIPY-forskolin (10 μmol/l), or tetramethylrhodamine-ethylester (TMRE) (10 μmol/l). Staining with fura-2 was performed by placing the islets in a serum-free culture medium (Dulbecco’s modified Eagle’s medium [DMEM]) containing 10 μmol/l fura-2-AM, 0.1% pluronic F127, and 0.1% bovine serum albumin for 30 min at 37°C and washing with solution A. These fluorescence indicators were purchased from Molecular Probes (Eugene, OR). BODIPY-forskolin and fura-2-acetoxymethyl were first dissolved in DMSO at high concentrations. An adenovirus vector for yellow cameleon 2.1 was constructed as described elsewhere (8–10). Adenovirus infection was performed on islets cultured for 1 day. The islets were placed in a serum-free culture medium (DMEM) containing the virus (5.7 × 108 pfu/ml) for 1 h, washed, and subsequently cultured for 2 days. Imaging experiments were then performed at room temperature (24.5–25.5°C).

    Multiphoton excitation imaging.

    Two-photon excitation imaging of islets was performed with an inverted microscope (IX70; Olympus, Tokyo) and a laser-scanning microscope (FluoView; Olympus) using a water immersion objective lens (UApo 60× water/IR) as described elsewhere (4). The laser power at the specimen was 3–10 mW. Lucifer yellow was excited at 720 nm, whereas sulforhodamine, yellow cameleon 2.1, FM1-43, BODIPY-forskolin, fura-2, and TMRE were excited at 830 nm. The fluorescence of indicators other than yellow cameleon 2.1 was measured with a photomultiplier of the laser-scanning microscope at wavelengths of 400–620 nm. The fluorescence of yellow cameleon 2.1 was measured at 400–510 nm (F480) and 530–650 nm (F530), and the ratio between F530 and F480 was calculated. Twelve-bit images were color-coded with either the autumn or green color codes of FluoView.

    RESULTS

    Hydrophilic probes.

    When acutely isolated islets were perifused with a solution containing hydrophilic tracers, such as lucifer yellow (Fig. 1A) or sulforhodamine (data not shown), highly fluorescent areas (Fig. 1A, the white arrow and arrowheads) and puncta (Fig. 1A, the blue arrow and arrowheads) quickly appeared within 30 s (Fig. 1B), which apparently reflected the major blood vessels and microvessels in the islets, respectively. In addition, we noted all the interstitial spaces of islets were subsequently filled with tracers (Fig. 1A, the green arrow and arrowheads; Fig. 1B). These structures were evenly stained between the inner as well as outer layers of islets, when images were obtained at planes within 20–50 μm of the bottom of an islet on a glass coverslip. Thus, two-photon excitation imaging can visualize deep cell layers (down to the third or fifth layers) in the islet. These staining patterns were preserved in islet preparations cultured for >6 days.

    The adenovirus vector can be transfected into deep cell layers of an islet. Figure 1C shows an islet transfected with an adenovector carrying the gene encoding yellow cameleon 2.1, a Ca2+ indicator protein based on green fluorescent protein (GFP) and calmodulin (11). Fluorescent expression was detected in the cells deep within the islet (Fig. 1C). The fact that expression levels of cameleon 2.1 greatly differ from cell to cell indicates that cameleon cannot penetrate the gap junctions (12). Furthermore, synchronous increases in the fluorescence ratio at 480 nm/530 nm were induced in many cells in the islet by application of a high-concentration potassium solution from a glass pipette, indicating that Ca2+ signaling is preserved after the virus infection. Thus, GFP-based Ca2+ indicator can monitor the cytosolic Ca2+ concentration of cells in deep layers of islets, unlike acetoxymethyl esters of organic Ca2+ indicators (Fig. 2E).

    Lipophilic probes.

    FM1-43 is a lipophilic yet membrane-impermeable tracer (13). We found that FM1-43 also brightly stained the islet blood vessels and the plasma membrane facing the interstitial space throughout the islet preparations within 3 min (Fig. 2A). The fluorescent intensity of blood vessels in the middle of the islets was as strong as those in the superficial layers (Fig. 2B), and there was little cytosolic staining within 20 min after application.

    In contrast, BODIPY-forskolin and fura-2-acetoxymethyl, which are lipophilic and membrane-permeable tracers, were accumulated in the superficial cell layers of the islets (Fig. 2C and E) and did not penetrate into deeper cell layers even 30 min to 2 h after the application (data not shown) (14). This result indicates that, even though these dyes are dissolved into solution by DMSO, they probably stick to the plasma membrane of cells in the superficial cell layers, are internalized, and do not readily leave the superficial cell layers. Therefore, the concentrations of substances that can reach the deeper cell layers can be very low. Lipophilic probes that have unusually high membrane permeability, however, were found to penetrate into deeper cell layers but over a longer period of time. For example, TMRE stained mitochondria throughout the islet 30 min after application.

    DISCUSSION

    We have demonstrated that various fluorescence probes can be successfully applied for two-photon excitation imaging of the whole-islet preparations. The rapid penetration of hydrophilic substances via blood vessels is consistent with nearly synchronous increases in NADH autofluorescence throughout the islet during high glucose stimulation (5). Direct visualization of islet interstitial space with either polar tracers or FM1-43 will provide a promising methodology for the direct imaging of insulin exocytosis in the whole-islet preparations.

    On the other hand, membrane-permeable fluorescence probes tend to get trapped in the superficial layer of the islets and exhibited steep concentration gradients along the depth axis of a single islet (Fig. 2D and F). Thus, the most efficient method for cytosolic loading of the cells in the islet seems to involve virus-mediated gene transfer. In fact, we have shown that an adenovirus carrying the cameleon 2.1 gene can induce expression of cameleon proteins in deep cell layers of islets and enable the detection of increase in cytosolic Ca2+ by depolarization (Fig. 1C), which was impossible with commonly used acetoxymethyl esters of organic Ca2+ indicators (Fig. 2E).

    It has been reported that insulin exocytosis from single β-cells shows high sensitivity to cytosolic cAMP (12,15). In contrast, cytosolic cAMP was claimed to play a less significant role in the whole-islet preparation because the membrane-permeable antagonist of cAMP, Rp-cAMP (16,17), or inhibitors (protein kinase inhibitors [PKIs]) of cAMP-dependent protein kinase (PKA) (9,10) showed relatively weak effects on glucose-induced insulin secretion. It needs to be noted, however, that Rp-cAMP did not sufficiently reach the deep cell layers of islets (18,19) and that the myristoylated PKI peptide (18) or PKI peptide in liposome (19,20) was trapped in the most superficial layers of islets. Direct evidence for the involvement of cAMP/PKA in insulin exocytosis will be gained either by using adenoviruses carrying cAMP/PKA inhibitory peptides or proteins or by using two-photon excitation imaging of insulin exocytosis in whole-islet preparations.

    FIG. 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIG. 1.

    Two-photon excitation imaging of islets of Langerhans with hydrophilic substances. A: An image of an islet immersed in lucifer yellow (1 mmol/l) for 30 s. The XY scanning was made at the plane 25 μm above the glass surface. B: Time courses of fluorescence intensity at four distinct areas: extra-islet (the red arrow and circle in A), major blood vessels (the white arrow and arrowheads in A), microvessels (the blue arrow and arrowheads in A), and interstitial spaces (the green arrow and arrowheads in A). Fluorescence values were obtained at the areas with the same size as the red circles and normalized with those at 150 s after the application of lucifer yellow. Each color of the traces reflects one of four distinct areas in A depicted by arrows. C: An image of an islet that was transfected with adenovirus carrying yellow cameleon 2.1. D: Time courses of fluorescence ratios for the two emission wavelengths (480 nm/530 nm) acquired at six areas depicted in C (a: red; b: orange; c: green; d: cyan; e: blue; f: black). The hatched bar indicates the period of application of 150 mmol/l KCl from a glass pipette to the islet.

    FIG. 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIG. 2.

    Two-photon excitation imaging of islets with lipophilic substances. Images of islets immersed for 10 min in FM1-43 (4 μmol/l) (A); BODIPY-forskolin (10 μmol/l) (C); and fura-2-AM (10 μmol/l) (E). B, D, and F: Fluorescence intensity profiles of the images shown in A, C, and E, respectively, at lines indicated by the arrows.

    Acknowledgments

    This work was supported by grants to H.K. from the Ministry of Education, Science, Sports, and Culture (ECSST) of Japan; the Research for the Future program of the Japan Society for the Promotion of Science; and CREST (Core Research for Evolutionary Science and Technology) of the Japan Science and Technology Corporation (JST). It was also supported by a grant to N.T. from the Tanabe Medical Frontier Conference and by grants to H.O. from ECSST and from CREST of the JST.

    We thank Drs. Atsushi Miyawaki and Roger Y. Tsien for providing us with a DNA construct of yellow cameleon 2.1, Drs. Izumu Saito and Yumi Kanegae for materials used in construction of recombinant adenoviruses, and Saki Ogawa for excellent technical support.

    Footnotes

    • Address correspondence and reprint requests to norikomd{at}nips.ac.jp.

      Accepted for publication 22 May 2001.

      DMEM, Dulbecco’s modified Eagle’s medium; GFP, green fluorescent protein; PKA, cAMP-dependent protein kinase; PKI, protein kinase inhibitor; TMRE, tetramethylrhodamine-ethylester.

      The symposium and the publication of this article have been made possible by an unrestricted educational grant from Servier, Paris.

    REFERENCES

    1. ↵
      Denk W, Strickler JH, Webb WW: Two-photon laser scanning fluorescence microscopy. Science 248: 73–76, 1990
      OpenUrlAbstract/FREE Full Text
    2. Yuste R, Denk W: Dendritic spines as basic functional units of neuronal integration. Nature 375:682–684, 1995
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      Svoboda K, Tank DW, Denk W: Direct measurement of coupling between dendritic spines and shafts. Science 272:716–719, 1996
      OpenUrlAbstract/FREE Full Text
    4. ↵
      Nemoto T, Kimura R, Ito K, Tachikawa A, Miyashita Y, Iino M, Kasai H: Sequential-replenishment mechanism of exocytosis in pancreatic acini. Nat Cell Biol 3:253–258, 2001
      OpenUrlCrossRefPubMedWeb of Science
    5. ↵
      Bennett BD, Jetton TL, Ying G, Magnuson MA, Piston DW: Quantitative subcellular imaging of glucose metabolism within intact pancreatic islets. J Biol Chem 271:3647–3651, 1996
      OpenUrlAbstract/FREE Full Text
    6. ↵
      Piston DW, Knobel SM, Postic C, Shelton KD, Magnuson MA: Adenovirus-mediated knockout of a conditional glucokinase gene in isolated pancreatic islets reveals an essential role for proximal metabolic coupling events in glucose-stimulated insulin secretion. J Biol Chem 274:1000–1004, 1999
      OpenUrlAbstract/FREE Full Text
    7. ↵
      Takahashi N, Kadowaki T, Yazaki Y, Miyashita Y, Kasai H: Multiple exocytotic pathways in pancreatic cells. J Cell Biol 138:55–64, 1997
      OpenUrlAbstract/FREE Full Text
    8. ↵
      Miyake S, Makimura M, Kanegae Y, Harada S, Sato Y, Takamori K, Tokuda C, Saito I: Efficient generation of recombinant adenoviruses using adenovirus DNA-terminal protein complex and a cosmid bearing the full-length virus genome. Proc Natl Acad Sci U S A 93:1320–1324, 1996
      OpenUrlAbstract/FREE Full Text
    9. ↵
      Kanegae Y, Makimura M, Saito I: A simple and efficient method for purification of infectious recombinant adenovirus. Jpn J Med Sci Biol 47:157–166, 1994
      OpenUrlCrossRefPubMed
    10. ↵
      Kanegae Y, Lee G, Sato Y, Tanaka M, Nakai M, Sakaki T, Sugano S, Saito I: Efficient gene activation in mammalian cells by using recombinant adenovirus expressing site-specific Cre recombinase. Nucleic Acids Res 23:3816–3821, 1995
      OpenUrlAbstract/FREE Full Text
    11. ↵
      Miyawaki A, Griesbeck O, Heim R, Tsien RY: Dynamic and quantitative Ca2+ measurements using improved cameleons. Proc Natl Acad Sci U S A 96:2135–2140, 1999
      OpenUrlAbstract/FREE Full Text
    12. ↵
      Ashcroft FM, Proks P, Smith P, Ammälä C, Bokvist K, Rorsman P: Stimulus-secretion coupling in pancreatic cells. J Cell Biochem 55 (Suppl.):54–65, 1994
    13. ↵
      Betz WJ, Bewick GS: Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255:200–203, 1992
      OpenUrlAbstract/FREE Full Text
    14. ↵
      Nadal A, Quesada I, Soria B: Homologous and heterologous asynchronicity between identified alpha-, beta- and delta-cells within intact islets of Langerhans in the mouse. J Physiol (Lond) 517:85–93, 1999
      OpenUrlCrossRefPubMedWeb of Science
    15. ↵
      Takahashi N, Kadowaki T, Yazaki Y, Ellis-Davies GCR, Miyashita Y, Kasai H: Post-priming actions of ATP in the Ca2+ dependent exocytosis in pancreatic β-cells. Proc Natl Acad Sci U S A 96:760–765, 1999
      OpenUrlAbstract/FREE Full Text
    16. ↵
      Sato Y, Henquin JC: The K+-ATP channel-independent pathway of regulation of insulin secretion by glucose: in search of the underlying mechanism. Diabetes 47:1713–1721, 1998
      OpenUrlAbstract
    17. ↵
      Persaud SJ, Jones PM, Howell SL: Glucose-stimulated insulin secretion is not dependent on activation of protein kinase A. Biochem Biophys Res Commun 173:833–839, 1990
      OpenUrlCrossRefPubMedWeb of Science
    18. ↵
      Harris TE, Persaud SJ, Jones PM: Pseudosubstrate inhibition of cyclic AMP-dependent protein kinase in intact pancreatic islets: effects on cyclic AMP-dependent and glucose-dependent insulin secretion. Biochem Biophys Res Commun 232:648–651, 1997
      OpenUrlCrossRefPubMedWeb of Science
    19. ↵
      Lester LB, Langeberg LK, Scott JD: Anchoring of protein kinase A facilitates hormone-mediated insulin secretion. Proc Natl Acad Sci U S A 94:14942–14947, 1997
      OpenUrlAbstract/FREE Full Text
    20. ↵
      Welsh N, Hallberg A, Sandler S, Hellerstrom C: Use of liposomes to introduce substances into pancreatic islet cells. Diabetes 37:1123–1128, 1988
      OpenUrlAbstract/FREE Full Text
    View Abstract
    PreviousNext
    Back to top

    In this Issue

    February 2002, 51(suppl 1)
    • Table of Contents
    • Index by Author
    Sign up to receive current issue alerts
    View Selected Citations (0)
    Print
    Download PDF
    Article Alerts
    Sign In to Email Alerts with your Email Address
    Email Article

    Thank you for your interest in spreading the word about Diabetes.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Two-Photon Excitation Imaging of Pancreatic Islets With Various Fluorescent Probes
    (Your Name) has forwarded a page to you from Diabetes
    (Your Name) thought you would like to see this page from the Diabetes web site.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Citation Tools
    Two-Photon Excitation Imaging of Pancreatic Islets With Various Fluorescent Probes
    Noriko Takahashi, Tomomi Nemoto, Ryoichi Kimura, Akira Tachikawa, Akiko Miwa, Haruo Okado, Yasushi Miyashita, Masamitsu Iino, Takashi Kadowaki, Haruo Kasai
    Diabetes Feb 2002, 51 (suppl 1) S25-S28; DOI: 10.2337/diabetes.51.2007.S25

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    Add to Selected Citations
    Share

    Two-Photon Excitation Imaging of Pancreatic Islets With Various Fluorescent Probes
    Noriko Takahashi, Tomomi Nemoto, Ryoichi Kimura, Akira Tachikawa, Akiko Miwa, Haruo Okado, Yasushi Miyashita, Masamitsu Iino, Takashi Kadowaki, Haruo Kasai
    Diabetes Feb 2002, 51 (suppl 1) S25-S28; DOI: 10.2337/diabetes.51.2007.S25
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Jump to section

    • Article
      • Abstract
      • RESEARCH DESIGN AND METHODS
      • RESULTS
      • DISCUSSION
      • Acknowledgments
      • Footnotes
      • REFERENCES
    • Figures & Tables
    • Info & Metrics
    • PDF

    Related Articles

    Cited By...

    More in this TOC Section

    • Effect of the Insulin Mimetic L-783,281 on Intracellular [Ca2+] and Insulin Secretion From Pancreatic β-Cells
    • Glucose-Dependent Promotion of Insulin Release From Mouse Pancreatic Islets by the Insulin-Mimetic Compound L-783,281
    • Role of Electrostatic and Hydrophobic Interactions in Ca2+-Dependent Phospholipid Binding by the C2A-Domain From Synaptotagmin I
    Show more Section 1: Insulin Release: Some Molecular Requisites

    Similar Articles

    Navigate

    • Current Issue
    • Online Ahead of Print
    • Scientific Sessions Abstracts
    • Collections
    • Archives
    • Submit
    • Subscribe
    • Email Alerts
    • RSS Feeds

    More Information

    • About the Journal
    • Instructions for Authors
    • Journal Policies
    • Reprints and Permissions
    • Advertising
    • Privacy Policy: ADA Journals
    • Copyright Notice/Public Access Policy
    • Contact Us

    Other ADA Resources

    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • Scientific Sessions Abstracts
    • Standards of Medical Care in Diabetes
    • BMJ Open - Diabetes Research & Care
    • Professional Books
    • Diabetes Forecast

     

    • DiabetesJournals.org
    • Diabetes Core Update
    • ADA's DiabetesPro
    • ADA Member Directory
    • Diabetes.org

    © 2021 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.