Target for diabetes treatment and prevention
The present invention relates to the identification of ALMS1 as the missing player involved in the regulation of the insulin-mediated glucose uptake through GLUT4 sorting vesicles, and to the down-regulation of ALMS1 by αPKC. Accordingly, the present invention relates to a molecule capable of preventing the binding of αPKC on ALMS1 for use for treating or preventing diabetes, in particular type 2 diabetes. In addition, the present invention relates to a method for identifying molecule capable of preventing the binding of αPKC on ALMS1.
1. A method of treating or delaying the progression or onset of diabetes mellitus, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, insulin resistance, hyperglycemia, obesity, and/or hyperinsulinaemia comprising administering a molecule inhibiting the binding of αPKC (Protein Kinase C alpha type) to ALMS1 (Alstrom syndrome protein 1) to a subject in need of treatment, wherein the molecule is a peptide, the peptide comprises a fragment of SEQ ID NO: 14, and said fragment is between 5 and 50 amino acids in length and spans one or more amino acid residue(s) selected from the group consisting of S227, S232, F262, D266, W267, K269, E271, G285, T296, V329, and I332 of SEQ ID NO: 14.
2. The method according to claim 1 , wherein said method treats or delays the progression or onset of type 2 diabetes mellitus in said subject.
3. The method according to claim 1 , wherein the molecule does not interfere with the binding of TBC1D4 to ALMS1.
4. The method according to claim 1 , wherein the peptide is between 5 and 20 amino acids in length.
5. The method according to claim 1 , wherein the peptide is a stapled peptide.
6. The method according to claim 1 , wherein the peptide is between 5 and 30 amino acids in length.