Glucagon-aP2 Binding Compounds for Dysregulated Hepatic Glucose
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Solution Overview
Problem
Current treatments for elevated blood glucose levels, non-alcoholic fatty liver disease (NAFLD), and diabetes are inadequate, and there is a need for new compounds and methods to address the underlying molecular mechanisms of these conditions.
Innovation Solution
Identify and design compounds that neutralize the glucagon receptor agonist glucagon in complex with its obligate binding partner adipocyte lipid binding protein (aP2) to inhibit glucagon signaling, using methods such as antibody binding to the glucagon/aP2 complex, thereby modulating glucose metabolism.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If current treatments (insulin, metformin) are used to manage elevated blood glucose, then blood glucose levels can be controlled, but the underlying molecular mechanisms remain unaddressed and treatment options are limited
Solution Approach 1:
The patent introduces compounds that target the glucagon/aP2 complex as an intermediary mechanism. These compounds bind to the glucagon receptor or the aP2 protein, disrupting the interaction between glucagon and its binding partner, thereby providing a new therapeutic pathway that addresses the root molecular cause of hyperglycemia rather than just managing symptoms
Solution Approach 2:
The patent modifies the biochemical parameters of glucose metabolism by targeting the glucagon signaling pathway. By changing the binding affinity or interaction dynamics between glucagon and aP2, the compounds alter hepatic glucose production and insulin sensitivity, providing a mechanism-based approach to treating metabolic disorders
2Use of energy by moving object
If glucagon signaling is activated to increase blood glucose, then energy availability is improved, but hepatic glucose production becomes dysregulated and blood glucose levels elevate abnormally
Solution Approach 1:
The patent converts the harmful effect of uncontrolled glucagon signaling into a beneficial therapeutic mechanism. By designing compounds that specifically target and disrupt the glucagon/aP2 complex, the invention transforms the previously harmful dysregulated glucose production into a controllable process, enabling treatment of hyperglycemia while preserving appropriate energy metabolism
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds effectively reduce hepatic glucose production and normalize blood glucose levels, providing therapeutic benefits for conditions like diabetes and NAFLD by disrupting the glucagon/aP2 complex, thus improving metabolic disorders.
Implementation Method 1
Identify and design compounds that neutralize the glucagon receptor agonist glucagon in complex with its obligate binding partner adipocyte lipid binding protein (aP2) to inhibit glucagon signaling
Implementation Method 2
using methods such as antibody binding to the glucagon/aP2 complex, thereby modulating glucose metabolism
Implementation Method 3
The compounds effectively reduce hepatic glucose production and normalize blood glucose levels, providing therapeutic benefits for conditions like diabetes and NAFLD by disrupting the glucagon/aP2 complex
Data Source
AI summary
The present invention provides a method to identify and use compounds for the inhibition of abnormal or dysregulated hepatic glucose production that results in elevated blood glucose levels and associated metabolic disorders. The invention is based on the surprising discovery that the glucagon forms an obligate binding complex with aP2, which is necessary for activation of the glucagon G-coupled protein receptor.