Delaying the progression of diabetes
Type-1 diabetes (T1 D) results from the autoimmune recognition of insulin producing β-cells within the pancreatic islet. The present application discloses a new protein, islet homeostasis protein (IHoP), that has a role in glucagon synthesizing-cell functions, and in post-onset T1 D islet differential expression of IHoP. Methods of delaying the onset of diabetes are disclosed, as well as compositions including an iHoP modulating agent. Also disclosed are methods of screening for iHoP modulating agents.
1. A method of ameliorating or delaying the onset of diabetes in a subject in need thereof, the method comprising administering a therapeutically effective amount of islet homeostasis protein (iHoP) modulating agent to said subject, wherein said iHoP modulating agent is a nucleic acid based inhibitor that targets an iHoP nucleic acid sequence.
2. The method of claim 1 , wherein said iHoP modulating agent is administered via parenteral, ocular, oral, rectal, lingual, transdermal or intravaginal administration.
3. The method of claim 1 , wherein said iHoP modulating agent is administered according to a regiment comprising daily dosage for a period of at least 24 hours, 48 hours, 3 days, 1 week or two weeks.
4. The method of claim 1 , wherein said iHoP modulating agent is administered in a composition that comprises a pharmaceutically acceptable carrier.
5. The method of claim 1 , wherein said patient in need exhibits at least one symptom comprising ketoacidosis, a state of metabolic dysregulation characterized by the smell of acetone; a rapid, deep breathing known as Kussmaul breathing; nausea; vomiting and abdominal pain; polyuria (frequent urination); polydipsia (increased thirst); polyphagia (increased hunger), increased or decreased insulin levels, or elevated serum glucose.
6. The method of claim 1 , wherein said patient in need exhibits impaired glucose tolerance.
7. The method of claim 6 , wherein said patient in need exhibits fasting glucose levels of 100 mg/dL to 125 mg/dL, or optionally fasting glucose levels above 125 mg/dL.
8. The method of claim 6 , wherein said patient in need exhibits plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g oral glucose load.
9. A method of treating diabetes in a patient in need, said method comprising administering a therapeutically effective amount of a composition comprising an islet homeostasis protein (iHoP) modulating agent, wherein said iHoP modulating agent is a nucleic acid based inhibitor that targets an iHoP nucleic acid sequence.
10. The method of claim 9 , wherein said iHoP modulating agent is administered via parenteral, ocular, oral, rectal, lingual, transdermal or intravaginal administration.
11. The method of claim 9 , wherein said iHoP modulating agent is administered according to a regiment comprising daily dosage for a period of at least two weeks.
12. The method of claim 9 , wherein said composition further comprises a pharmaceutically acceptable carrier.
13. The method of claim 9 , wherein said patient in need exhibits one or more of the following symptoms:
Fasting plasma glucose level ≧7.0 mmol/L (126 mg/dL);
Plasma glucose ≧11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test;
Symptoms of hyperglycemia and casual plasma glucose ≧11.1 mmol/L (200 mg/dL); or
Glycated hemoglobin (Hb A1C) ≧6.5%.
14. The method of claim 13 , wherein said patient in need exhibits two or more of the stated symptoms.
15. The method of claim 1 , wherein the modulating agent is administered via introduction of a delivery vector to the patient.
16. The method of claim 1 , wherein the modulating agent is an RNA interfering molecule targeting iHoP.