What Is an Islet and Its Function in the Body?

Islets are tiny clusters of hormone-producing cells embedded throughout the pancreas, and their primary job is regulating blood sugar. Formally called the islets of Langerhans, after the German medical student Paul Langerhans who first described them in 1869, these cellular clusters make up only about one to two percent of the pancreas by volume, yet they are responsible for producing insulin, glucagon, and several other hormones that keep your blood glucose within a narrow, livable range. When islets malfunction or get destroyed, the result is diabetes and a cascade of metabolic problems that affect virtually every organ system.

Where Islets Sit in the Pancreas

Your pancreas is a roughly six-inch-long organ tucked behind the stomach, and most of its tissue is devoted to producing digestive enzymes. The islets are scattered throughout this digestive tissue like small islands in a sea, which is exactly why Langerhans chose the name. A single human pancreas contains somewhere around one to two million of these clusters, though the number varies considerably from person to person.

They are not evenly distributed. Three-dimensional mapping of healthy human pancreases has shown that islets tend to be grouped more tightly in the head of the pancreas and gradually disperse toward the tail.¹ At the same time, the tail region has roughly double the islet density of the head and body, and it contains a higher proportion of large islets.² On average, the ratio of endocrine cell mass from head to body to tail runs about 1:1:2.³ This uneven distribution matters surgically: if a surgeon needs to remove part of the pancreas, taking the tail means losing a disproportionate share of islet tissue.

The Cell Types Inside an Islet

Each islet is a miniature organ containing several types of endocrine cells, each producing a different hormone. The main cast includes:

• Beta cells: the most abundant, producing insulin, which lowers blood sugar.
• Alpha cells: produce glucagon, which raises blood sugar.
• Delta cells: produce somatostatin, a hormone that acts as a brake on both insulin and glucagon release.
• PP cells: produce pancreatic polypeptide, which influences appetite and digestive function.
• Epsilon cells: a rare population that produces ghrelin, a hunger-signaling hormone.

If you have seen textbook diagrams showing beta cells neatly packed in the center of an islet with alpha and delta cells forming an outer ring, that picture comes mostly from rodent studies. Human islets look different. The endocrine cells are more randomly mixed throughout the cluster, and more than 70 percent of human beta cells are in direct physical contact with other cell types.⁴ Smaller human islets resemble the tidy rodent pattern more closely, while larger ones have a distinct, more complex architecture.⁵ This matters because drug and therapy development has long relied on mouse models, and the structural differences between mouse and human islets mean that findings in mice do not always translate to people.

How Islets Regulate Blood Sugar

The core function of islets is to act as a biological thermostat for glucose. After you eat, rising blood sugar triggers beta cells to release insulin. Between meals or during exercise, falling blood sugar prompts alpha cells to release glucagon. The two hormones work in opposition, keeping glucose in a range that your brain, muscles, and other tissues can use safely.

Beta cells sense glucose directly. When glucose enters a beta cell, it gets metabolized in the cell’s mitochondria, raising levels of ATP. That rise in ATP triggers a chain of electrical events at the cell membrane that ultimately lets calcium flood in, and the calcium spike causes insulin-containing granules to fuse with the cell surface and spill their contents into the bloodstream.⁶ Without functional mitochondria, beta cells cannot respond to glucose at all, even though they can still release insulin if the membrane is artificially triggered.⁷ Other nutrients like fatty acids and amino acids do not trigger insulin release on their own, but they amplify the response when glucose is already elevated.⁸

Glucagon release from alpha cells follows a mirror-image logic. When glucose levels fall, a signaling molecule called cAMP rises inside alpha cells, directly stimulating glucagon secretion. Researchers have shown this glucose-sensing mechanism works independently of signals from neighboring beta cells: alpha cells can detect low glucose on their own and respond accordingly.⁹ A specific receptor on alpha cells, the adenosine A2A receptor, plays a key role in ensuring sufficient glucagon release when blood sugar drops to dangerously low levels.¹⁰

Crosstalk Between Islet Cells

Islets are not just a collection of independent cells happening to sit near each other. They function as tightly coordinated units where each cell type communicates with its neighbors through an elaborate signaling network. The hormones themselves serve double duty: insulin does not just leave the islet to lower blood sugar elsewhere; it also acts locally to restrain glucagon release from nearby alpha cells. Somatostatin from delta cells inhibits both insulin and glucagon secretion, serving as a kind of volume knob for the whole cluster.¹¹

On top of hormonal crosstalk, islet cells also communicate using neurotransmitters more commonly associated with the brain. Alpha cells co-release glutamate alongside glucagon, which stimulates neighboring cells. Beta cells release GABA, which inhibits alpha cells while activating other beta cells.¹² This means the islet operates with both hormonal and neural-style communication layered on top of each other, creating a redundancy that helps fine-tune hormone output from moment to moment. Researchers studying human islets have emphasized that this signaling picture is turning out to be considerably more complex than previously appreciated, and that results from rodent studies do not reliably predict how human islet cells talk to each other.¹³

The Blood Supply and Nerve Connections

For such small structures, islets receive a strikingly generous blood supply. Islet blood flow is far higher per unit of tissue than the blood flow to the surrounding digestive pancreas, and the capillaries inside islets are densely packed and fenestrated, meaning they have small pores that allow rapid exchange of nutrients and hormones.¹⁴ This rich vascular network is not passive plumbing. Blood flow through the islets is actively regulated by the nervous system, by chemical signals from the endothelium lining the blood vessels, and by metabolic signals from the beta cells themselves.¹⁵ Human islets even contain smooth muscle-lined blood vessels not found in rodent islets, another structural difference that complicates cross-species research.⁴

Islets are also wired into the autonomic nervous system. Sympathetic nerve fibers, which release noradrenaline and other signaling molecules, reach into the islet and make direct contact with alpha and delta cells. This allows the brain and spinal cord to modulate hormone release during stress, exercise, or the fight-or-flight response. The exact wiring pattern in human islets has been debated, with earlier two-dimensional studies suggesting sparse innervation and more recent three-dimensional imaging revealing more extensive nerve contacts than previously thought.¹⁶

What Happens When Islets Fail

The two major forms of diabetes each involve a distinct kind of islet breakdown, and understanding the difference matters for treatment.

In type 1 diabetes, the immune system attacks and destroys beta cells specifically, leaving alpha, delta, and other islet cells largely intact. The immune assault involves multiple arms of the immune system, including T cells and macrophages, and appears to be triggered when beta cells display certain self-proteins on their surfaces that the immune system misidentifies as foreign.¹⁷ Several beta cell proteins have been identified as targets, including insulin itself and an enzyme called glutamic acid decarboxylase.¹⁸ Once enough beta cells are gone, the person can no longer produce sufficient insulin and needs it from an external source.

Type 2 diabetes involves a different trajectory. Beta cells are not destroyed by immune attack but instead gradually lose function and die over time. A key player in this process is a protein called islet amyloid polypeptide (IAPP), which beta cells normally co-secrete alongside insulin. In type 2 diabetes, IAPP aggregates into sticky, fibrous deposits called amyloid within the islets. These deposits are toxic to beta cells and are thought to be a major contributor to the progressive loss of beta cell mass seen in the disease.¹⁹ Autopsies of people with type 2 diabetes have found roughly a 20 to 50 percent reduction in beta cell mass, but the functional impairment is typically greater than that loss alone would explain, suggesting that the amyloid formation process damages surviving cells before killing them.²⁰ Aggregated IAPP is also a concern in islet transplantation: when donor islets are transplanted into people with type 1 diabetes, amyloid deposits can form in the grafted tissue and damage it over time.²¹

Islet Tumors

Rarely, islet cells can form tumors. The most well-known type is an insulinoma, a tumor of beta cells that pumps out insulin uncontrollably, driving blood sugar dangerously low. Insulinomas affect an estimated one to four people per million and are the most common functioning islet cell tumor.²² Symptoms often include sweating, tremor, and heart palpitations from the body’s adrenaline response to low sugar, along with neurological effects like confusion, personality changes, and seizures caused by the brain being starved of glucose. These symptoms can mimic psychiatric or neurological disorders for months or years before the tumor is identified, so recognizing the pattern of repeated low blood sugar episodes is the critical first step toward diagnosis.²³ Most insulinomas are small and benign, and surgical removal is usually curative.

Islet Transplantation and Stem Cell Approaches

Because type 1 diabetes is caused by the loss of beta cells, one logical treatment strategy is to replace them. Islet transplantation involves taking islet clusters from a deceased donor’s pancreas, purifying them, and infusing them into a recipient’s liver through a catheter. The islets lodge in the liver’s small blood vessels and begin producing insulin. The landmark Edmonton Protocol, developed in 2000, showed that this approach could work, and 20-year follow-up data have confirmed its long-term safety.²⁴

The procedure is not without significant limitations, though. In the international trial of the Edmonton Protocol, about 44 percent of recipients met the primary goal of good blood sugar control one year after transplantation, and while 58 percent achieved insulin independence at some point, three-quarters of those people needed insulin again within two years.²⁵ Recipients must also take immunosuppressive drugs for life to prevent their immune system from destroying the transplanted islets, and the supply of donor pancreases is far smaller than the number of people who could benefit. Multiple donors are often needed for a single recipient, making the scarcity problem even worse.

This is why stem cell-derived islets have generated so much excitement. Researchers can now coax pluripotent stem cells through a series of developmental stages to create islet-like cell clusters in the lab. Recent work has demonstrated a full pipeline from growing these clusters in bioreactors to encapsulating them in protective alginate beads and transplanting them into animals, where they showed glucose-responsive insulin secretion and remained functional for up to 98 days.²⁶ The encapsulation strategy is particularly interesting because if the coating can shield the cells from the immune system, recipients might not need lifelong immunosuppression.²⁷ This technology is still early-stage, but it addresses both of the Edmonton Protocol’s main bottlenecks at once: donor scarcity and immune rejection.

Islets Can Adapt to Changing Demands

Islets are not static structures. They can grow and shrink in response to metabolic demand, and one of the most striking examples of this plasticity occurs during pregnancy. As the growing fetus and placenta increase the mother’s insulin resistance, beta cells compensate by multiplying and becoming more active, increasing overall insulin output to maintain normal blood sugar.²⁸ After delivery, this expansion reverses and the beta cell mass returns toward its pre-pregnancy state. When this adaptation fails to keep pace with demand, gestational diabetes results.²⁹ The fact that beta cells can expand and contract in response to physiological cues is one reason researchers are so interested in understanding the signals that drive this process, because harnessing them could potentially stimulate beta cell regeneration in people with diabetes.

Islets Across the Animal Kingdom

Pancreatic islets are not unique to humans. They appear across vertebrates, though their composition has become more complex over evolutionary time. The most basic version is found in larval lampreys, which have an islet organ containing only one hormone-producing cell type (beta cells, making insulin). Hagfish have two cell types, adult lampreys have three, and most other fish and all land vertebrates have the full four-cell-type islet with beta, alpha, delta, and PP cells.³⁰ Even earlier in evolutionary history, before discrete islets existed, the same types of hormone-producing cells were scattered through the walls of the digestive tract in simple chordates. The islet, in other words, is an evolutionary innovation that concentrated previously dispersed hormonal control into a compact, efficient organ within an organ.

Imaging Islets in Living People

One of the longstanding challenges in islet research has been the inability to see islets in a living person. They are too small and too scattered for standard medical imaging to resolve individually. This means that in diabetes research and clinical care, doctors have had to rely on indirect measures like blood insulin or C-peptide levels to estimate how much functional beta cell mass a patient has left.

That picture is starting to change. A promising technique uses manganese-enhanced MRI to measure functional beta cell mass without surgery or biopsy. Manganese is taken up by metabolically active beta cells, providing a signal that correlates with their function. In one study, healthy volunteers showed pancreatic manganese uptake roughly two to three times higher than people with type 1 diabetes who had very low insulin production, and the uptake correlated strongly with C-peptide levels in people with diabetes.³¹ The technique showed strong reproducibility across repeated scans and between different observers reading the images. If validated further, this kind of imaging could allow researchers to track beta cell loss in real time during early-stage diabetes, monitor responses to experimental treatments, and identify people who are losing beta cells before they develop symptoms. Other approaches using PET scanning are also under investigation, though all of these methods remain research tools rather than routine clinical tests for now.³²

Why Islets Get Named After Langerhans

Paul Langerhans was a 22-year-old medical student in Berlin when he described these clusters in 1869, though he did not know what they did. It took decades for other researchers to connect the islets to blood sugar control. In 1909, the term “insulin” was coined for the hypothetical molecule believed to originate from these islets and regulate glucose, though the substance itself had not yet been isolated.³³ That breakthrough came in 1921, when the Canadian surgeon Frederick Banting and medical student Charles Best succeeded in extracting insulin for the first time. Banting and the laboratory director J.J.R. Macleod received the Nobel Prize for the achievement two years later. The gap between Langerhans’ anatomical observation and the functional understanding of what islets actually do spans half a century, a reminder of how slowly biological puzzles sometimes yield their secrets even when a critical piece is sitting in plain view under a microscope.