<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04432090</url>
  </required_header>
  <id_info>
    <org_study_id>1552172</org_study_id>
    <nct_id>NCT04432090</nct_id>
  </id_info>
  <brief_title>Study of the Pharmacologic Action of a GPR119 Agonist on Glucagon Counter-regulation During Insulin-induced Hypoglycemia in Type 1 Diabetes Mellitus</brief_title>
  <acronym>PHROG</acronym>
  <official_title>A Randomized, Placebo-controlled, Double-blinded Cross-over Study of the Pharmacologic Action of a GPR119 Agonist on Glucagon Counter-regulation During Insulin-induced Hypoglycemia in Type 1 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AdventHealth Translational Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AdventHealth Translational Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test if a specific research medication could increase the&#xD;
      response to low blood glucose in people with type 1 diabetes. The response of the body to low&#xD;
      blood sugar will be measured in healthy people as a reference point.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 21, 2021</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">November 11, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal glucagon concentration during hypoglycemia</measure>
    <time_frame>Day 14, Day 28, 6 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total area under the curve (AUC) for glucagon during hypoglycemia.</measure>
    <time_frame>Day 14, Day 28, 6 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incremental AUC for glucagon during hypoglycemia (above baseline levels during euglycemia)</measure>
    <time_frame>Day 14, Day 28, 6 hours</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>MBX-2982 first then placebo- Volunteers with Type 1 diabetes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This will be followed by a second study period in which they will be crossed over to the other treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>this group will not receive any medication. It will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo first then MBX-2982- Volunteers with Type 1 diabetes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)</description>
    <arm_group_label>MBX-2982 first then placebo- Volunteers with Type 1 diabetes</arm_group_label>
    <arm_group_label>Placebo first then MBX-2982- Volunteers with Type 1 diabetes</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Study Medication (MBX-2982)</intervention_name>
    <description>Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)</description>
    <arm_group_label>MBX-2982 first then placebo- Volunteers with Type 1 diabetes</arm_group_label>
    <arm_group_label>Placebo first then MBX-2982- Volunteers with Type 1 diabetes</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No medication for this group</intervention_name>
    <description>This group will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.</description>
    <arm_group_label>Healthy Volunteers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Type 1 diabetes cohort&#xD;
&#xD;
          1. Age &gt;20 years&#xD;
&#xD;
          2. Diagnosis of T1DM according to American Diabetes Association (ADA) criteria&#xD;
             continuously requiring insulin for survival&#xD;
&#xD;
          3. Diabetes diagnosis performed more than 5 years before enrollment&#xD;
&#xD;
          4. Fasting C-peptide levels &lt; 0.7 ng/mL with a concurrent plasma glucose concentration &gt;&#xD;
             90 mg/dL&#xD;
&#xD;
          5. For female participants: agrees not to become pregnant during the study and for at&#xD;
             least 2 weeks after the last dose of the study medication. For male participants:&#xD;
             agrees not to donate sperm or not to get a woman pregnant during the study and for at&#xD;
             least 2 weeks after the last dose of the study medication.&#xD;
&#xD;
        Healthy subject cohort&#xD;
&#xD;
          1. Age &gt;20 years&#xD;
&#xD;
          2. General good health&#xD;
&#xD;
          3. Creatinine clearance &gt;80 mL/min based on MDRD equation&#xD;
&#xD;
          4. Fasting blood glucose (FBG) &gt;70 mg/dL and &lt;100 mg/dL&#xD;
&#xD;
          5. No history of diabetes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. BMI &gt;30 kg/m2 and &lt;18.5 kg/m2&#xD;
&#xD;
          2. No evidence by history, EKG or exams of symptomatic cardiovascular disease (unstable&#xD;
             angina, myocardial infarction or coronary revascularization within 6 months,&#xD;
             clinically significant abnormalities on EKG, presence of cardiac pacemaker, implanted&#xD;
             cardiac defibrillator)&#xD;
&#xD;
          3. Evidence of autonomic neuropathy&#xD;
&#xD;
          4. Liver disease (AST or ALT &gt;2.5 times the upper limit of normal)&#xD;
&#xD;
          5. Kidney disease (creatinine &gt;1.6 mg/dl or estimated GFR &lt;60 ml/min).&#xD;
&#xD;
          6. Dyslipidemia, including triglycerides &gt;500 mg/dl, LDL &gt;200 mg/dl or unstable&#xD;
             hyperlipidemia. Treatment with a single lipid lowering agents is allowed if stable&#xD;
             within the previous 3 months.&#xD;
&#xD;
          7. Anemia (hemoglobin &lt;12 g/dl in men, &lt;11 g/dl in women)&#xD;
&#xD;
          8. Thyroid dysfunction (suppressed thyroid stimulating hormone (TSH), elevated TSH &lt;10&#xD;
             µIU/ml if symptomatic or elevated TSH &gt;10 µIU/ml if asymptomatic)&#xD;
&#xD;
          9. Uncontrolled hypertension (BP &gt;160 mmHg systolic or &gt;100 mmHg diastolic) or treatment&#xD;
             with more than 2 antihypertensive medications&#xD;
&#xD;
         10. History of cancer within the last 5 years (skin cancers, with the exception of&#xD;
             melanoma, may be acceptable).&#xD;
&#xD;
         11. History of organ transplant&#xD;
&#xD;
         12. History of HIV, active Hepatitis B or C, or Tuberculosis&#xD;
&#xD;
         13. Pregnancy, lactation or 6 months postpartum from the scheduled date of collection&#xD;
&#xD;
         14. Females of childbearing potential (any female except those with tubal ligation,&#xD;
             hysterectomy, or absence of menses &gt;2 years) unwilling to use an approved method of&#xD;
             contraception (one medically accepted method of contraception with ≥99% effectiveness&#xD;
             when used consistently and correctly: implantable uterine device (IUD), hormonal&#xD;
             contraception). Male participants: unwilling to use appropriate contraception (e.g.&#xD;
             condoms) and/or their partner uses a medically accepted form of contraception during&#xD;
             the study.&#xD;
&#xD;
         15. History of Major Depression in the last 5 years&#xD;
&#xD;
         16. History of an eating disorder&#xD;
&#xD;
         17. History of bariatric surgery&#xD;
&#xD;
         18. History of drug or alcohol abuse (&gt; 3 drinks per day) within the last 5 years&#xD;
&#xD;
         19. Psychiatric disease prohibiting adherence to study protocol&#xD;
&#xD;
         20. Use of oral or injectable anti-hyperglycemic agents: metformin, sulfonylureas, DPP IV&#xD;
             inhibitors, SGLT-2 inhibitors, thiazolidinediones, acarbose, GLP-1 analogs&#xD;
&#xD;
         21. Current use of beta-adrenergic blocking agents or their use was stopped less than one&#xD;
             month before recruitment&#xD;
&#xD;
         22. Initiation or change in hormone replacement therapy within the past 3 months&#xD;
             (including, but not limited to thyroid hormone or estrogen replacement therapy)&#xD;
&#xD;
         23. Use of any medications known to influence glucose, fat and/or energy metabolism within&#xD;
             the last 3 months (e.g., growth hormone therapy, glucocorticoids [steroids],&#xD;
             prescribed medications for weight loss, etc.)&#xD;
&#xD;
         24. Current night shift worker&#xD;
&#xD;
         25. Presence of any condition that, in the opinion of the Investigator, compromises&#xD;
             participant safety or data integrity or the participant's ability to complete study&#xD;
             visits Additional exclusion Criteria for type 1 diabetes cohort&#xD;
&#xD;
         26. History of T2DM or any form of diabetes other than T1DM&#xD;
&#xD;
         27. Hypoglycemia unawareness as assessed using the GOLD score&#xD;
&#xD;
         28. Using a predictive low blood glucose suspend mode on an insulin pump or a hybrid&#xD;
             closed loop algorithm for insulin delivery. For those applying these strategies for&#xD;
             everyday management of blood glucose and willing to participate, the algorithm will be&#xD;
             stopped at enrollment where possible.&#xD;
&#xD;
         29. Two or more episode of severe hypoglycemia per month in the past six months.&#xD;
&#xD;
         30. QTcF &gt;450 ms for males and &gt;470 ms for females&#xD;
&#xD;
         31. Using non-insulin agents to control blood glucose levels.&#xD;
&#xD;
         32. No evidence of moderate or severe end-organ diabetic complications of retinopathy,&#xD;
             nephropathy or neuropathy. Non-proliferative retinopathy and microalbuminura will be&#xD;
             allowed.&#xD;
&#xD;
             Additional exclusion Criteria for the healthy cohort&#xD;
&#xD;
         33. Insulin treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Pratley, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Study Principal Investigator</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AdventHealth Translational Research Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ekberg JH, Hauge M, Kristensen LV, Madsen AN, Engelstoft MS, Husted AS, Sichlau R, Egerod KL, Timshel P, Kowalski TJ, Gribble FM, Reiman F, Hansen HS, Howard AD, Holst B, Schwartz TW. GPR119, a Major Enteroendocrine Sensor of Dietary Triglyceride Metabolites Coacting in Synergy With FFA1 (GPR40). Endocrinology. 2016 Dec;157(12):4561-4569. doi: 10.1210/en.2016-1334. Epub 2016 Oct 25.</citation>
    <PMID>27779915</PMID>
  </reference>
  <reference>
    <citation>Flock G, Holland D, Seino Y, Drucker DJ. GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms. Endocrinology. 2011 Feb;152(2):374-83. doi: 10.1210/en.2010-1047. Epub 2010 Nov 10.</citation>
    <PMID>21068156</PMID>
  </reference>
  <reference>
    <citation>Lauffer LM, Iakoubov R, Brubaker PL. GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes. 2009 May;58(5):1058-66. doi: 10.2337/db08-1237. Epub 2009 Feb 10.</citation>
    <PMID>19208912</PMID>
  </reference>
  <reference>
    <citation>Li NX, Brown S, Kowalski T, Wu M, Yang L, Dai G, Petrov A, Ding Y, Dlugos T, Wood HB, Wang L, Erion M, Sherwin R, Kelley DE. GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia. Diabetes. 2018 Jul;67(7):1401-1413. doi: 10.2337/db18-0031. Epub 2018 Apr 18.</citation>
    <PMID>29669745</PMID>
  </reference>
  <reference>
    <citation>Segerstolpe A, Palasantza A, Eliasson P, Andersson EM, Andreasson AC, Sun X, Picelli S, Sabirsh A, Clausen M, Bjursell MK, Smith DM, Kasper M, Ammala C, Sandberg R. Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes. Cell Metab. 2016 Oct 11;24(4):593-607. doi: 10.1016/j.cmet.2016.08.020. Epub 2016 Sep 22.</citation>
    <PMID>27667667</PMID>
  </reference>
  <reference>
    <citation>Bolli G, Calabrese G, De Feo P, Compagnucci P, Zega G, Angeletti G, Cartechini MG, Santeusanio F, Brunetti P. Lack of glucagon response in glucose counter-regulation in type 1 (insulin-dependent) diabetics: absence of recovery after prolonged optimal insulin therapy. Diabetologia. 1982 Feb;22(2):100-5. doi: 10.1007/BF00254837.</citation>
    <PMID>7037510</PMID>
  </reference>
  <reference>
    <citation>Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science. 1973 Oct 12;182(4108):171-3. doi: 10.1126/science.182.4108.171.</citation>
    <PMID>4581053</PMID>
  </reference>
  <reference>
    <citation>Gerich JE. Lilly lecture 1988. Glucose counterregulation and its impact on diabetes mellitus. Diabetes. 1988 Dec;37(12):1608-17. doi: 10.2337/diab.37.12.1608.</citation>
    <PMID>3056759</PMID>
  </reference>
  <reference>
    <citation>Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes. 1997 Feb;46(2):271-86.</citation>
    <PMID>9000705</PMID>
  </reference>
  <reference>
    <citation>Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol. 2014 Dec;10(12):711-22. doi: 10.1038/nrendo.2014.170. Epub 2014 Oct 7.</citation>
    <PMID>25287289</PMID>
  </reference>
  <reference>
    <citation>UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007 Jun;50(6):1140-7. doi: 10.1007/s00125-007-0599-y. Epub 2007 Apr 6.</citation>
    <PMID>17415551</PMID>
  </reference>
  <reference>
    <citation>Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2013 Jul 25;369(4):362-72. doi: 10.1056/NEJMra1215228. No abstract available.</citation>
    <PMID>23883381</PMID>
  </reference>
  <reference>
    <citation>Rizza RA, Cryer PE, Gerich JE. Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. Effects of somatostatin and combined alpha- and beta-adrenergic blockade on plasma glucose recovery and glucose flux rates after insulin-induced hypoglycemia. J Clin Invest. 1979 Jul;64(1):62-71. doi: 10.1172/JCI109464.</citation>
    <PMID>36413</PMID>
  </reference>
  <reference>
    <citation>Yue JT, Burdett E, Coy DH, Giacca A, Efendic S, Vranic M. Somatostatin receptor type 2 antagonism improves glucagon and corticosterone counterregulatory responses to hypoglycemia in streptozotocin-induced diabetic rats. Diabetes. 2012 Jan;61(1):197-207. doi: 10.2337/db11-0690. Epub 2011 Nov 21.</citation>
    <PMID>22106159</PMID>
  </reference>
  <reference>
    <citation>Szewczyk JW, Acton J, Adams AD, Chicchi G, Freeman S, Howard AD, Huang Y, Li C, Meinke PT, Mosely R, Murphy E, Samuel R, Santini C, Yang M, Zhang Y, Zhao K, Wood HB. Design of potent and selective GPR119 agonists for type II diabetes. Bioorg Med Chem Lett. 2011 May 1;21(9):2665-9. doi: 10.1016/j.bmcl.2010.12.086. Epub 2010 Dec 22.</citation>
    <PMID>21273063</PMID>
  </reference>
  <reference>
    <citation>Christensen M, Calanna S, Sparre-Ulrich AH, Kristensen PL, Rosenkilde MM, Faber J, Purrello F, van Hall G, Holst JJ, Vilsboll T, Knop FK. Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes. Diabetes. 2015 Jan;64(1):72-8. doi: 10.2337/db14-0440. Epub 2014 Jul 22.</citation>
    <PMID>25053587</PMID>
  </reference>
  <reference>
    <citation>Davis SN, Mann S, Briscoe VJ, Ertl AC, Tate DB. Effects of intensive therapy and antecedent hypoglycemia on counterregulatory responses to hypoglycemia in type 2 diabetes. Diabetes. 2009 Mar;58(3):701-9. doi: 10.2337/db08-1230. Epub 2008 Dec 10.</citation>
    <PMID>19073776</PMID>
  </reference>
  <reference>
    <citation>Farngren J, Persson M, Schweizer A, Foley JE, Ahren B. Vildagliptin reduces glucagon during hyperglycemia and sustains glucagon counterregulation during hypoglycemia in type 1 diabetes. J Clin Endocrinol Metab. 2012 Oct;97(10):3799-806. doi: 10.1210/jc.2012-2332. Epub 2012 Aug 1.</citation>
    <PMID>22855332</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04432090
org study id: 1552172
nct id: NCT04432090
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to test if a specific research medication could increase the
      response to low blood glucose in people with type 1 diabetes. The response of the body to low
      blood sugar will be measured in healthy people as a reference point.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Maximal glucagon concentration during hypoglycemia
time frame: Day 14, Day 28, 6 hours
measure: Total area under the curve (AUC) for glucagon during hypoglycemia.
time frame: Day 14, Day 28, 6 hours
measure: Incremental AUC for glucagon during hypoglycemia (above baseline levels during euglycemia)
time frame: Day 14, Day 28, 6 hours
arm group label: MBX-2982 first then placebo- Volunteers with Type 1 diabetes
arm group type: Experimental
description: This will be followed by a second study period in which they will be crossed over to the other treatment.
arm group label: Healthy Volunteers
arm group type: Active Comparator
description: this group will not receive any medication. It will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.
arm group label: Placebo first then MBX-2982- Volunteers with Type 1 diabetes
arm group type: Experimental
intervention type: Drug
intervention name: Placebo
description: Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)
arm group label: MBX-2982 first then placebo- Volunteers with Type 1 diabetes
arm group label: Placebo first then MBX-2982- Volunteers with Type 1 diabetes
intervention type: Drug
intervention name: Study Medication (MBX-2982)
description: Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)
arm group label: MBX-2982 first then placebo- Volunteers with Type 1 diabetes
arm group label: Placebo first then MBX-2982- Volunteers with Type 1 diabetes
intervention type: Other
intervention name: No medication for this group
description: This group will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.
arm group label: Healthy Volunteers
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Richard Pratley, MD
role: Principal Investigator
affiliation: Study Principal Investigator
facility: 
country: United States
citation: Ekberg JH, Hauge M, Kristensen LV, Madsen AN, Engelstoft MS, Husted AS, Sichlau R, Egerod KL, Timshel P, Kowalski TJ, Gribble FM, Reiman F, Hansen HS, Howard AD, Holst B, Schwartz TW. GPR119, a Major Enteroendocrine Sensor of Dietary Triglyceride Metabolites Coacting in Synergy With FFA1 (GPR40). Endocrinology. 2016 Dec;157(12):4561-4569. doi: 10.1210/en.2016-1334. Epub 2016 Oct 25.
PMID: 27779915
citation: Flock G, Holland D, Seino Y, Drucker DJ. GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms. Endocrinology. 2011 Feb;152(2):374-83. doi: 10.1210/en.2010-1047. Epub 2010 Nov 10.
PMID: 21068156
citation: Lauffer LM, Iakoubov R, Brubaker PL. GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes. 2009 May;58(5):1058-66. doi: 10.2337/db08-1237. Epub 2009 Feb 10.
PMID: 19208912
citation: Li NX, Brown S, Kowalski T, Wu M, Yang L, Dai G, Petrov A, Ding Y, Dlugos T, Wood HB, Wang L, Erion M, Sherwin R, Kelley DE. GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia. Diabetes. 2018 Jul;67(7):1401-1413. doi: 10.2337/db18-0031. Epub 2018 Apr 18.
PMID: 29669745
citation: Segerstolpe A, Palasantza A, Eliasson P, Andersson EM, Andreasson AC, Sun X, Picelli S, Sabirsh A, Clausen M, Bjursell MK, Smith DM, Kasper M, Ammala C, Sandberg R. Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes. Cell Metab. 2016 Oct 11;24(4):593-607. doi: 10.1016/j.cmet.2016.08.020. Epub 2016 Sep 22.
PMID: 27667667
citation: Bolli G, Calabrese G, De Feo P, Compagnucci P, Zega G, Angeletti G, Cartechini MG, Santeusanio F, Brunetti P. Lack of glucagon response in glucose counter-regulation in type 1 (insulin-dependent) diabetics: absence of recovery after prolonged optimal insulin therapy. Diabetologia. 1982 Feb;22(2):100-5. doi: 10.1007/BF00254837.
PMID: 7037510
citation: Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science. 1973 Oct 12;182(4108):171-3. doi: 10.1126/science.182.4108.171.
PMID: 4581053
citation: Gerich JE. Lilly lecture 1988. Glucose counterregulation and its impact on diabetes mellitus. Diabetes. 1988 Dec;37(12):1608-17. doi: 10.2337/diab.37.12.1608.
PMID: 3056759
citation: Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes. 1997 Feb;46(2):271-86.
PMID: 9000705
citation: Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol. 2014 Dec;10(12):711-22. doi: 10.1038/nrendo.2014.170. Epub 2014 Oct 7.
PMID: 25287289
citation: UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007 Jun;50(6):1140-7. doi: 10.1007/s00125-007-0599-y. Epub 2007 Apr 6.
PMID: 17415551
citation: Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2013 Jul 25;369(4):362-72. doi: 10.1056/NEJMra1215228. No abstract available.
PMID: 23883381
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responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Hypoglycemia
sharing ipd: No