# US 2014/0193361 A1 · Systemic glucose tolerance in type-2 diabetes > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0193361 A1 - Document ID: US20140193361A1 - Status: Published application - Kind: A1 - Application number: 14/241,482 - Filed: 2012-08-30 - Published: 2014-07-10 - Earliest claimed: 2011-08-30 - Assignees: Cornell University - Inventors: Ling Qi; Yewei JI - Web page: https://patentgrep.com/patent/US20140193361A1 ## CPC - A61K 38/2086: {IL-13 to IL-16} - A61K 31/7028: Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages - A61K 31/7032: attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides - A61K 38/19: Cytokines; Lymphokines; Interferons - A61K 38/2026: {IL-4} - A61K 38/2066: {IL-10} - A61K 38/208: {IL-12} - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/50: for increasing or potentiating the activity of insulin - C12N 5/0646: {Natural killers cells [NK], NKT cells} - C12Q 1/6851: Quantitative amplification - G01N 33/505: {involving T-cells} - G01N 33/5088: {of vertebrates} - G01N 33/6863: {Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors} - G01N 33/6869: {Interleukin} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Obesity is associated with a state of chronic low-grade inflammation and the present invention establishes that adipose-resident natural killer T (NKT) cells attenuate inflammation in adipose tissue and improves systemic glucose homeostasis in mice at different stages of obesity. Accordingly, the present invention provides methods of treating type-2 diabetes or those at risk for type-2 diabetes using activators of adipose-resident NKT cells. Such activators include particular glycolipids (e.g., a-galactosyl-ceramide and its analogs other than sulfated analogs) and cytokines that promote M2 macrophage polarization. The invention also includes methods to screen for activators of adipose-resident NKT cells. ## Claims ### Claim 1 A method for treating an individual having type-2 diabetes or at risk for type-2 diabetes which comprises administering an activator of adipose-resident NKT cells for a time and in an amount to improve glucose tolerance or to decrease insulin resistance in said individual. ### Claim 2 (depends on 1) The method of claim 1, wherein said activator is α-galactosylceramide. ### Claim 3 (depends on 1) The method of claim 1, wherein said activator is an analog of α-galactosylceramide with the proviso that said analog is not sulfatide or a sulfatide analog. ### Claim 4 (depends on 1) The method of claim 1, wherein said activator is IL-4, IL-12 or IL-13. ### Claim 5 (depends on 1) The method of claim 1, wherein said activator promotes M2 macrophage polarization. ### Claim 6 (depends on 1) The method of claim 1, wherein said activator is a TH2 cytokine. ### Claim 7 (depends on 6) The method of claim 6, wherein said cytokine is selected from the group consisting of IL-4, IL-10, IL-12 or IL-13. ### Claim 8 An isolated population of mammalian adipose-resident type-1 NKT cells, said population having at least 50% to about 80% CD4−CD8− type-1 NKT cells and about 20 to 30% CD4+CD8− type-1 NKT cells. ### Claim 9 (depends on 8) The population of claim 8 wherein said cells are murine or human. ### Claim 10 A method to screen for an activator of adipose-resident NKT cells which comprises (a) preparing an isolated population of adipose-resident type-1 NKT; (b) contacting said cells with a candidate activator for a time sufficient to induce said cells to release a TH2 cytokine; and (c) detecting whether said cells have produced increased levels of a TH2 cytokine relative to untreated adipose-resident NKT cells. ### Claim 11 (depends on 11) The method of claim 11, wherein increased levels of said cytokine is detected by a northern blot, by a nucleic acid hybridization technique, by RNA-Seq, by PCR, by ELISA, by immunoblotting or by immunohistochemical staining. ### Claim 12 A method to screen for an activator of adipose-resident NKT cells which comprises (a) preparing an isolated population of adipose-resident type-1 NKT; (b) contacting said cells with a candidate activator for a time sufficient to promote M2 macrophage polarization; and (c) detecting whether said cells have increased expression, relative to untreated adipose-resident NKT cells, of an M2 gene selected from any one or more of the group consisting of Arginase 1 (Arg1), chitinase 3-like 3 (Chi3l3), C-type lectin domain family 7, member a (Clec7a), Programmed cell death 1 ligand 2 (Pdc1Ig2), Resistin like alpha (Retnla), Interleukin 1 receptor antagonist (Il1rn), and Interleukin receptor 4 alpha (Il4ra). ### Claim 13 (depends on 12) The method of claim 12, wherein increased expression is detected by a northern blot, by a nucleic acid hybridization technique, by RNA-Seq, by PCR, by ELISA, by immunoblotting or by immunohistochemical staining. ### Claim 14 A method to screen for an activator of adipose-resident NKT cells which comprises (a) feeding one or more mice a high fat diet (HFD) for at least about 4 days up to about 24 weeks; (b) administering a candidate activator to said one or more mice; (c) sacrificing said one or more mice from about 4 to about 7 days after administering said activator; (d) preparing white adipose tissue (WAT) from said mice; and (e) detecting whether (i) said WAT contains increased expression, relative to expression in WAT from control mice, of any one or more of IL4, IL13, IL12, Arg1, Chi3l3, Clec71, Pdcd1Ig2, Retnla, Il1m and Il4ra, (ii) M2 macrophage polarization increases in said WAT relative to that in WAT from control mice, and/or (iii) whether one or more TH2 cytokine are produced. ### Claim 15 (depends on 14) The method of claim 14, wherein increased expression is detected by a northern blot, by a nucleic acid hybridization technique, by RNA-Seq, by PCR, by ELISA, by immunoblotting or by immunohistochemical staining. ### Claim 16 (depends on 14) The method of claim 14, wherein said mice are wild-type mice or have a genetic predisposition to obesity.