# Metabolic Functions of Pyruvate Kinase M2 in Pancreatic Beta Cells

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $338,651

## Abstract

Abstract
Over 375 million people suffer from type 2 diabetes (T2D), a disease defined by the failure of pancreatic β-cells.
Insulin secretion and maintenance of endoplasmic reticulum (ER) Ca²+ levels are two essential β-cell functions
known to fail in T2D. Therefore, uncovering the metabolic regulatory pathways critical to these processes will
allow the development of new therapies for T2D. We propose that modulation of the glycolytic enzyme pyruvate
kinase (PK) has strong potential to be of protective and therapeutic value. We have discovered that of the three
PK isoforms in the β-cell, activation of PKM2 both potentiates insulin secretion and raises ER Ca²+ levels. The
objective of the research described in this application is to use novel metabolic imaging methods to identify the
specific steps in the β-cell metabolic and secretory pathways that are controlled by PKM2, and to determine the
extent to which PKM2 activation can protect/restore insulin secretion and ER Ca²+ during diabetes progression.
To do so, we will: 1) Determine how PKM2 regulates the triggering and metabolic amplifying pathways of insulin
secretion, 2) Determine the role of PKM2 in ER Ca²+ homeostasis and the neurohormonal amplification of insulin
secretion, and 3) Assess the contribution of impaired PKM2 activity to diabetes pathophysiology and the
therapeutic potential of PKM2 activation. Completion of these aims will heighten our understanding of nutrient
signaling in the pancreatic β-cell, and evaluate promising new targets for the prevention and therapy of T2D.

## Key facts

- **NIH application ID:** 10135918
- **Project number:** 5R01DK113103-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Matthew J. Merrins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,651
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135918

## Citation

> US National Institutes of Health, RePORTER application 10135918, Metabolic Functions of Pyruvate Kinase M2 in Pancreatic Beta Cells (5R01DK113103-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135918. Licensed CC0.

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