# Test of catestatin (CST) and its mimetic as a new therapy for type 2 diabetes (T2D)

> **NIH NIH R43** · SIRAJ THERAPEUTICS INC. · 2023 · $306,100

## Abstract

Over 130 million Americans are either diabetic or pre-diabetic. A significant fraction of them is obese or
overweight. There are seven classes of diabetic therapies against type II diabetes available including insulin
therapy. But all these drugs are associated with some side effects including the danger of hypoglycemia.
Therefore, more options to treat T2D are needed. We found that Catestatin (CST) and its analog, retro-inverso
(RI)-CST have anti-diabetic properties. CST is a Chromogranin A-derived peptide that improves insulin sensitivity
and reduces blood glucose levels in diet-induced obese (DIO) mouse model of diabetes by acting on multiple
pathways including anti-inflammatory and glucose metabolism. Its anti-inflammatory activity prevents the
infiltration of pro-inflammatory macrophages in the liver. It inhibits gluconeogenesis and glycogenolysis but
induces glycogenesis. Also notable is that CST and RI-CST can be administered orally, and plasma CST appears
within 15 min with a half-life of around 7 hrs. These remarkable properties position CST and RI-CST as highly
potential diabetes therapies which we plan to investigate in this proposal. We further plan to investigate the
therapeutic potential of CST and its mimic RI-CST as combination therapies. All currently used diabetes therapy
is associated with side effects which include gastrointestinal, cardiovascular, pancreatitis, polyurea,
angioedema, and LDL cholesterol. We hypothesize that toxic side effects of currently used diabetes medicine
will be minimized if their doses can be lowered which can be accomplished by the addition of CST. Indeed, our
preliminary results confirm our hypothesis where we found two-fold lower amounts of TZD are more effective
when used in combination with CST than the regular dose of TZD alone. We propose two aims: in Aim 1, we
plan to investigate the absorption and tissue distribution of RI-CST and determine the toxicity of both CST and
RI-CST in mice. In aim 2, we plan to investigate the effectiveness of both mono and combination therapy of CST
and RI-CST.

## Key facts

- **NIH application ID:** 10823055
- **Project number:** 1R43DK138733-01
- **Recipient organization:** SIRAJ THERAPEUTICS INC.
- **Principal Investigator:** Shandy Shahabi
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $306,100
- **Award type:** 1
- **Project period:** 2023-09-25 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823055

## Citation

> US National Institutes of Health, RePORTER application 10823055, Test of catestatin (CST) and its mimetic as a new therapy for type 2 diabetes (T2D) (1R43DK138733-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10823055. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*