Trpv1 + sensory neurons control of beta-cell stress and islet inflammation in diabetes

Abstract

A process is disclosed for controlling inflammatory tissue access through release of neuropeptides, such as substance P (sP), to insulin-responsive sensory neurons, whereby simultaneous control of insulin sensitivity/resistance is manifested. In models of Type 1 and Type 2 diabetes, sensory afferents, in particular TRPV1, have fundamental roles in insulin/glucose homeostasis, islet physiology and autoimmune tissue inflammation. By manipulation of the TRPV1 neuro-β-cell circuit or enhancement of pancreatic sP levels, normalization of insulin resistance, clearance of inflammation and prevention of both Type 1 and Type 2 diabetes is realized.

1 - 6 . (canceled) 
     
     
         7 . A method comprising the following steps:
 (a) identifying a mammal having any one or more of the following: hyperinsulinism, insulin deficiency, high blood glucose levels, abnormal insulin resistance, glucose intolerance, pancreatic islet inflammation, or pancreatic islet infiltration of T cells; and   (b) administering to said mammal a composition comprising a sensory afferent neuron neuropeptide.   
     
     
         8 . The method of  claim 7 , wherein said mammal has diabetes or prediabetes. 
     
     
         9 . The method of  claim 8 , wherein said mammal has Type 1 diabetes (T1D). 
     
     
         10 . The method of  claim 8 , wherein said mammal has Type 2 diabetes (T2D). 
     
     
         11 . The method of  claim 7 , wherein said mammal is a human. 
     
     
         12 . The method of  claim 7 , wherein said sensory afferent neuron neuropeptide is substance P (sP). 
     
     
         13 . The method of  claim 7 , wherein said composition is administered in step (b) via intra-arterial (i.a.) injection. 
     
     
         14 . The method of  claim 7 , wherein said composition comprises an amount of said sensory afferent neuron neuropeptide effective to reduce insulin resistance or enhance insulin sensitivity in said mammal. 
     
     
         15 . The method of  claim 7 , wherein said composition comprises an amount of said sensory afferent neuron neuropeptide effective to reduce or normalize blood glucose levels in said mammal. 
     
     
         16 . The method of  claim 7 , wherein said composition comprises an amount of said sensory afferent neuron neuropeptide effective to reduce inflammation or T cell infiltration in the pancreatic islet of said mammal. 
     
     
         17 . A method comprising the following steps:
 (a) identifying a mammal having any one or more of the following: hyperinsulinism, insulin deficiency, high blood glucose levels, abnormal insulin resistance, glucose intolerance, pancreatic islet inflammation, or pancreatic islet infiltration of T cells; and   (b) administering to said mammal a composition comprising a capsaicinoid compound.   
     
     
         18 . The method of  claim 17 , wherein said mammal has diabetes or prediabetes. 
     
     
         19 . The method of  claim 18 , wherein said mammal has Type 1 diabetes (T1D). 
     
     
         20 . The method of  claim 18 , wherein said mammal has Type 2 diabetes (T2D). 
     
     
         21 . The method of  claim 17 , wherein said mammal is a human. 
     
     
         22 . The method of  claim 17 , wherein said capsaicinoid compound is capsaicin. 
     
     
         23 . The method of  claim 17 , wherein said composition is administered in step (b) via intra-arterial (i.a.) injection. 
     
     
         24 . The method of  claim 17 , wherein said composition comprises an amount of said capsaicinoid compound effective to reduce insulin resistance or enhance insulin sensitivity in said mammal. 
     
     
         25 . The method of  claim 17 , wherein said composition comprises an amount of said capsaicinoid compound effective to reduce or normalize blood glucose levels in said mammal. 
     
     
         26 . The method of  claim 17 , wherein said composition comprises an amount of said capsaicinoid compound effective to reduce inflammation or T cell infiltration in the pancreatic islet of said mammal.