Can the Pancreas Regenerate Insulin Again?

The pancreas does retain some ability to produce insulin, even in people who have lived with diabetes for decades, and researchers are now closing in on several ways to amplify or restore that ability. The story is more encouraging than it was even five years ago: clinical trials of lab-grown insulin-producing cells have already freed some people with type 1 diabetes from daily injections for a year or more. But the full picture involves immune barriers, safety hurdles, and a gap between what works in a mouse and what works in a person.

The Pancreas Never Completely Gives Up

One of the most striking findings in recent diabetes research is that the insulin-producing cells of the pancreas, called beta cells, are not always wiped out as thoroughly as once thought. In type 1 diabetes, the immune system attacks and destroys beta cells, and for a long time the assumption was that this destruction was essentially total after the first few years. That assumption has been challenged. A study of people who had lived with type 1 diabetes for an average of roughly 35 years found that about 7.5% still showed meaningful insulin secretion in response to a meal stimulus, while another 5% showed low but detectable levels.¹ A separate study using a simpler urine test found that nearly half of people with type 1 diabetes had detectable C-peptide, a molecule released in equal amounts to insulin and used as a proxy for how much insulin the body is still making.²

When researchers have examined pancreatic tissue directly, the picture fills in further. Autopsies of people with long-duration type 1 diabetes have found scattered insulin-producing cells in every pancreas examined. Most had at least a few insulin-positive cells within some islets, and a subset had lobes containing multiple islets with numerous insulin-producing cells.³ These leftover cells are not producing enough insulin to matter clinically on their own, but their existence raises a tantalizing question: could the right intervention coax them to multiply?

Why Type 2 Diabetes Is a Different Problem

In type 2 diabetes, the loss of insulin production follows a different path, and the prospects for recovery are in some ways more straightforward. Rather than being killed off by the immune system, beta cells in type 2 diabetes appear to lose their identity. They undergo a process called dedifferentiation, reverting from mature, insulin-secreting cells to an earlier, less specialized state. Research in animal models has shown that this dedifferentiation, rather than cell death, is the primary reason beta cells stop making insulin in type 2 diabetes.⁴ The same research found that when blood sugar was brought back under control with insulin therapy, many of those dedifferentiated cells regained their mature identity and started producing insulin again.

This concept is now well supported. Dedifferentiated beta cells lose the molecular switches that define them as insulin producers and begin expressing markers normally seen only during early pancreatic development.⁵ The encouraging implication is that in type 2 diabetes, the cells are often still there; they just need the right signals to snap back into action. Aggressive blood sugar control, weight loss, and certain medications can help reverse this process, which is partly why some people with early type 2 diabetes achieve remission through lifestyle changes or bariatric surgery.

The Problem With Growing New Beta Cells Naturally

If residual beta cells exist, why can’t they simply divide and replenish themselves? The short answer is that beta cell replication slows to a crawl after childhood. In both humans and rodents, beta cells proliferate during the newborn period and early life, then undergo an age-dependent decline in their ability to divide. There are exceptions: the metabolic demands of pregnancy can trigger a temporary burst of beta cell growth, and insulin resistance prompts some compensatory expansion. But outside those circumstances, adult beta cells are remarkably reluctant to divide.⁶

This age-related decline is a major reason diabetes typically worsens over time rather than stabilizing. If the body could freely grow new beta cells throughout adulthood, both type 1 and type 2 diabetes would look very different. Finding ways to override that built-in brake on beta cell proliferation has been one of the central goals of regenerative diabetes research.

Drug Combinations That Push Beta Cells to Divide

Researchers have made real progress on the proliferation problem using drug combinations. One approach targets an enzyme called DYRK1A. Small molecules that block DYRK1A can nudge adult human beta cells to start dividing, but the rates are modest on their own, around 2%, and the effect is not specific to beta cells. The breakthrough came when researchers combined DYRK1A inhibitors with a second class of drugs. Pairing any DYRK1A inhibitor with any GLP-1 receptor agonist, a class of drugs already widely used to treat type 2 diabetes, produced a synergistic jump in beta cell replication to roughly 5-6%, accompanied by an actual increase in the number of human beta cells.⁷

A different drug pairing achieved similar results. Combining DYRK1A inhibitors with drugs that block TGF-beta signaling produced dramatic increases in beta cell proliferation, and the effect extended across multiple members of each drug class, not just one specific pair.⁸ These findings are still in the preclinical stage, meaning they have been demonstrated in human beta cells in lab dishes and in transplanted human islets in mice, not yet in human patients. But the principle that adult human beta cells can be pushed to divide is no longer in doubt.

GLP-1 receptor agonists, which include drugs like semaglutide and liraglutide, have an additional benefit beyond promoting proliferation: a meta-analysis of preclinical studies found they significantly reduce beta cell death.⁹ Protecting existing beta cells while encouraging new ones to grow is a two-pronged strategy that could eventually slow or halt the decline of insulin production.

Fasting-Mimicking Diets and Beta Cell Rebirth

One of the more surprising findings in this field involves dietary interventions. In mouse studies, cycles of a fasting-mimicking diet, which involves several days of very low calorie intake followed by normal eating, have triggered the pancreas to generate new beta cells. The mechanism resembles what happens during embryonic development: the diet activates a cascade of gene expression that leads to the creation of new insulin-producing cells from progenitor-like cells.¹⁰ In mouse models of both type 1 and type 2 diabetes, these fasting cycles restored insulin secretion and normalized blood sugar.

Follow-up work has confirmed that fasting and refeeding cycles increase markers of islet plasticity in the pancreas, meaning the cells show signs of being able to shift between identities.¹¹ Separate research found that intermittent fasting-mimicking diet cycles prevented the deterioration of islets in diabetic mice, increased the expression of beta cell progenitor markers, and reduced fasting blood sugar in a type 1 diabetes model.¹²

A word of caution: all of this work has been done in rodents. Mouse pancreases are not human pancreases, and the leap from animal models to clinical proof is one that many promising findings fail to make. People with diabetes should not attempt extended fasting without medical supervision, and these results do not yet justify any specific dietary protocol for beta cell regeneration in humans.

Growing Beta Cells in the Lab

The most dramatic clinical advances have come not from coaxing the body’s own pancreas to regrow, but from manufacturing insulin-producing cells outside the body and transplanting them in. Researchers have developed methods to turn human stem cells into functional beta cells in the lab, including from the stem cells of people who themselves have type 1 diabetes. These lab-grown beta cells express the right molecular markers, respond to glucose, and when transplanted into diabetic mice, they prevent diabetes and respond to anti-diabetic drugs.¹³

This technology has now reached human trials with remarkable early results. A trial of zimislecel, a product made from stem cell-derived islet cells, enrolled 14 people with type 1 diabetes who had no detectable insulin production at baseline. After receiving an infusion of these cells into the liver’s blood supply, all 14 showed evidence of engraftment and islet function. By one year, ten of the twelve participants who had reached that milestone, or 83%, were insulin-independent and no longer using injections.¹⁴ Earlier data from the same program had shown that even at half the target cell dose, the first patients infused achieved restored insulin production and glucose control, with one maintaining insulin independence.¹⁵

These results represent a genuine breakthrough, the first demonstration that lab-grown islet cells can functionally replace destroyed beta cells in humans with type 1 diabetes. The participants still require immunosuppressive drugs to prevent their bodies from rejecting the transplanted cells, which is a serious tradeoff, but the proof of concept is now established.

Converting Other Pancreatic Cells Into Beta Cells

Another approach sidesteps the need for outside cell sources entirely by reprogramming cells already living in the pancreas. Alpha cells, which normally produce glucagon (the hormone that raises blood sugar), sit right next to beta cells in the islets. Researchers have found that by switching off two specific genes in mouse alpha cells, they can convert a large fraction of them into cells that closely resemble beta cells. In one study, about half of the targeted alpha cells lost their original identity and began producing insulin along with other markers typical of native beta cells.¹⁶ This conversion happened directly, without the cells passing through a stem-cell-like intermediate stage, which reduces the risk of tumor formation.

The appeal of this strategy is obvious: the raw material already exists in the patient’s own body, and converted cells would presumably be recognized as self, potentially avoiding the immune rejection problem. The challenge is delivering the genetic changes safely and specifically to alpha cells in a living person without affecting other tissues. That remains an unsolved engineering problem, though advances in gene therapy delivery systems are gradually narrowing the gap.

The Immune System Stands in the Way

For people with type 1 diabetes, every regeneration strategy runs into the same wall: the immune system that destroyed the original beta cells will attack new ones too. This is true whether the new cells come from a lab, from a donor, from a pig, or from the patient’s own reprogrammed alpha cells if they display the molecular targets the immune system has learned to recognize. Both the autoimmune attack specific to type 1 diabetes and conventional transplant rejection threaten any replacement cells.¹⁷

Current clinical trials manage this with immunosuppressive drugs, the same kind of medications used after organ transplants. These drugs work, as the zimislecel trial demonstrates, but they carry real costs: increased susceptibility to infections, potential kidney damage over decades, and a slightly elevated cancer risk. For most people with well-managed type 1 diabetes, swapping daily insulin for lifelong immunosuppression is not clearly a better deal.

This is why a large research effort is focused on immune evasion. One strategy uses CRISPR gene editing to create “hypoimmune” beta cells, cells that have been genetically modified to be invisible to the immune system by knocking out or altering the surface molecules that immune cells use to identify targets.¹⁸ Another approach involves physically shielding transplanted cells inside tiny capsules made from biocompatible materials. These capsules let glucose and insulin pass through but block immune cells from reaching the beta cells inside. Neither strategy has been proven in large human trials yet, but both could eventually eliminate the need for immunosuppression.

Bioprinting and the Artificial Islet

One of the reasons lab-grown beta cells do not always work as well as natural ones is that they mature in isolation, missing the complex environment of a real pancreatic islet. In the body, beta cells sit alongside other cell types, blood vessels, nerve fibers, and a scaffold of supporting proteins, all of which send signals that influence how well the beta cells function. Researchers are now trying to recreate that environment using 3D bioprinting. By printing stem cell-derived islet cells together with blood vessel cells and allowing them to self-assemble, teams have produced structures that more closely mimic natural islets and show significantly better insulin secretion. One study found that bioprinted islet-vascular constructs showed roughly a 3.8-fold increase in insulin release under high glucose conditions compared to randomly assembled cells.¹⁹

Separately, co-printing human islet cell aggregates with blood vessel cells has been shown to recapitulate the shape and development of real human islets, with enhanced expression of both islet and vascular markers and improved glucose-stimulated insulin secretion.²⁰ The goal is to eventually produce transplantable islet tissue that arrives pre-vascularized and functionally mature, rather than relying on the body to build blood supply after transplantation.

Pig Islets as a Bridge

Even with advances in stem cell manufacturing, producing enough cells for every person who needs them is an enormous logistical challenge. Pig islets have long been studied as a potential alternative because pigs can be bred in large numbers and their islets function similarly to human ones. Preclinical studies have demonstrated long-term survival of pig islets in primates without evidence of the viral transmission that was once a major concern.²¹ These results have led to the development of clinical trial protocols for transplanting pig islets into humans.

The rejection problem is even more intense with cross-species transplants than with human donor cells, but CRISPR editing is being used to create genetically modified pigs whose islets are less recognizable to the human immune system.²² If these “humanized” pig islets can avoid rejection without heavy immunosuppression, they could provide a scalable cell source far sooner than manufactured stem cell products become affordable for the broader population.

Safety Concerns That Remain

Stem cell-based therapies carry a specific risk that does not apply to most other medical treatments: the potential for uncontrolled cell growth. Any time cells are grown from a pluripotent stage, there is a risk that some of them will form tumors called teratomas. Early experiments made this danger vivid: when embryonic stem cell-derived insulin-producing cells were transplanted into diabetic mice, they reversed the high blood sugar for about three weeks before immature teratomas developed and the treatment failed.²³ More recent manufacturing protocols, including the one used in the zimislecel trial, employ fully differentiated cells rather than partially mature ones, which dramatically reduces but does not entirely eliminate this concern.²⁴

Cost is another barrier. Manufacturing stem cell-derived islets at clinical scale requires sophisticated facilities and quality controls. Health technology assessments have flagged that manufacturing optimization is necessary to bring upfront costs down to a level where these therapies could be widely accessible.²⁵ A one-time cure for type 1 diabetes would likely save money over a lifetime of insulin, devices, and complication management, but the price tag of a single treatment could be staggering in the near term, raising questions about who gets access first.

How Doctors Measure What Is Left

If you have diabetes and are wondering how much insulin production you still have, the standard test measures C-peptide, a molecule that is co-produced with insulin in a one-to-one ratio. C-peptide is the best available measure of endogenous insulin secretion because, unlike insulin itself, it is not cleared quickly by the liver and is not confused with injected insulin.²⁶ A fasting blood draw can detect baseline levels, while a stimulated test taken after a mixed meal gives a fuller picture of how much the pancreas can ramp up production in response to food.

Knowing your residual beta cell function is not just academic. People with type 1 diabetes who retain some insulin production tend to spend more time in their target blood sugar range and experience fewer dangerous lows.² Even a small amount of surviving beta cell function acts as a buffer, smoothing out the swings that make diabetes management so difficult. Preserving whatever function remains, whether through early immunotherapy, tight glucose control, or future pharmacological strategies, is increasingly recognized as a meaningful clinical goal in its own right, separate from the more ambitious aim of full regeneration.