Glucagon and Insulin are both hormones produced and excreted by the same organ, the pancreas. There are regions in the pancreas called the islets of Langerhans where you can find the alpha cells responsible for producing Glucagon and the beta cells that produce Insulin. These two hormones work in tandem to maintain healthy levels of blood glucose.
Under normal circumstances, the level of insulin is determined by the amount of glucose in the blood plasma. So, when blood sugar rises the beta cells in the pancreas are triggered to release insulin so that glucose can be transported to our cells for energy. When blood sugar levels are low, the circulation of insulin ceases. This response is what is needed to maintain blood glucose levels within a normal narrow range.
“Glucose homeostasis: roles of insulin and glucagon. 1A. For nondiabetic individuals in the fasting state, plasma glucose is derived from glycogenolysis under the direction of glucagon (1). Basal levels of insulin control glucose disposal (2). Insulin’s role in suppressing gluconeogenesis and glycogenolysis is minimal due to low insulin secretion in the fasting state (3). 1B. For nondiabetic individuals in the fed state, plasma glucose is derived from ingestion of nutrients (1). In the bi-hormonal model, glucagon secretion is suppressed through the action of endogenous insulin secretion (2). This action is facilitated through the paracrine route (communication within the islet cells) (3). Additionally, in the fed state, insulin suppresses gluconeogenesis and glycogenolysis in the liver (4) and promotes glucose disposal in the periphery (5). 1C. For individuals with diabetes in the fasting state, plasma glucose is derived from glycogenolysis and gluconeogenesis (1) under the direction of glucagon (2). Exogenous insulin (3) influences the rate of peripheral glucose disappearance (4) and, because of its deficiency in the portal circulation, does not properly regulate the degree to which hepatic gluconeogenesis and glycogenolysis occur (5). 1D. For individuals with diabetes in the fed state, exogenous insulin (1) is ineffective in suppressing glucagon secretion through the physiological paracrine route (2), resulting in elevated hepatic glucose production (3). As a result, the appearance of glucose in the circulation exceeds the rate of glucose disappearance (4). The net effect is postprandial hyperglycemia (5).”1
Whereas insulin secretion is triggered by high blood sugar, the presence of Glucagon is initiated by low blood glucose levels. It prompts the liver to start breaking down sugar stored there in the form of glycogen. Once glycogen is broken down to glucose, it is then released into the bloodstream where it is transported to cells with the help of insulin for energy production. In certain situations, glucagon can induce the liver and muscles to synthesize glucose from non-carbohydrate sources such as proteins.
“The β-cells respond to many nutrients in the blood circulation, including glucose, other monosaccharides, amino acids, and fatty acids. Glucose is evolutionarily the primary stimuli for insulin release in some animal species, because it is a principal food component and can accumulate immediately after food ingestion. Indeed, in rodents and humans, the amplitude of insulin secretion induced by glucose is much larger compared with that stimulated by protein or fat. Oral ingestion of 75 g of glucose will cause plasma insulin to rise from a basal level (20–30 pmol/L) to 250–300 pmol/L in 30 min, while intake of a similar amount of fat or a fat plus protein diet will only increase plasma insulin levels to 50 and 60 pmol/L, respectively, in human subjects. While glucose is the obligate fuel source for neurons, other cells, including β-cells can use alternative fuel sources during brief periods of starvation, an adaptation that could predispose them to glucolipotoxicity.”2
From the foregoing, insulin has two main functions in the body
Promotes entry of glucose into the cells and also supports the synthesis of lipids. This essentially ‘mops’ up excess sugar from the plasma glucose.
Prevents mechanisms that would flood the bloodstream with excess glucose. This includes inhibition of glycogen, lipids and protein breakdown. It also prevents the buildup of ketone bodies which usually happens when fats are broken down for energy. — KETOACIDOSIS
“Until recently, insulin was the only pancreatic β-cell hormone known to lower blood glucose concentrations. Insulin, a small protein composed of two polypeptide chains containing 51 amino acids, is a key anabolic hormone that is secreted in response to increased blood glucose and amino acids following ingestion of a meal. Like many hormones, insulin exerts its actions through binding to specific receptors present on many cells of the body, including fat, liver, and muscle cells. The primary action of insulin is to stimulate glucose disappearance.”3
The function of Glucagon
Glucagon is a hormone that responds to low blood glucose levels by breaking down the macromolecule glycogen into the smaller molecules we know as glucose and releasing it into the bloodstream. Glucagon brings blood sugar up while Insulin brings blood sugar down.
Induces lipolysis which is the breakdown of lipids into free fatty acids.
“Glucagon is part of a homeostatic hormonal system developed to protect against serious decreases in blood glucose—glucose ‘counter-regulation’. This mechanism is the combination of processes that act to protect against the development of hypoglycaemia and (should this occur) restore normoglycaemia. Hypoglycaemia suppresses insulin secretion from β-cells and stimulates glucagon secretion from islet α-cells, normalizing blood glucose levels. Even small changes in glucagon can greatly increase blood glucose; the addition of minimal doses of glucagon (0.50 ng/kg/min) is known to induce long-lasting hyperglycaemia. Glucagon acts exclusively on the liver, where it stimulates both glycogenolysis (the breakdown of glycogen into glucose) and gluconeogenesis (the formation of new glucose molecules), increasing glucose output within minutes. Under certain conditions, glucagon can also stimulate production of ketone bodies in the liver, which during fasting or prolonged hypoglycaemia may substitute partially for glucose in meeting the brain’s energy needs.”4
“When the circulating glucose level rises, glucagon secretion is suppressed. This is likely to be via the reduction of P/Q-type Ca2+ channel activity in α-cells. Such inhibitory effect can be achieved by lowering the amplitude or the firing frequency of APs, by influencing membrane depolarization or repolarization, respectively. The change of membrane potential is a result of glucose metabolism or transport (via electrogenic sodium-glucose co-transporter 2 transporters), which leads to the alteration of membrane ion conductance. α-Cells are equipped with ATP-sensitive K+ channels (KATP channels) of the same molecular identity as in β-cells. Increasing glucose concentrations result in increased glucose metabolism and ATP production, inhibiting the KATP channel. This in turn leads to membrane depolarization. Consequently, the amplitude of APs reduces due to voltage-dependent inactivation of Nav channels. As a result, APs, although still being generated, cannot reach the voltage that is sufficient to open P/Q-type Ca2+ channels. The result is that secretion of glucagon is reduced.”5
“The glucose control of glucagon secretion from α-cells via intrinsic mechanisms. (A) KATP channels and SGLT2 depolarize the cell, decreasing action potential height and therefore P/Q activity. This results in reduced glucagon secretion. (B) TASK1 and store-operated channels (SOC) have been proposed to increase repolarizations in the cell, decreasing action potential frequency, and therefore glucagon secretion.”6
Terminology used to describe levels of Insulin
It refers to insulin levels in the blood that are lower than what is considered normal. This situation leads to insufficient glucose uptake by the body cells and subsequent rise in blood sugar. Many patients with diabetes type 2 experience low insulin levels. The primary reason for this is usually a problem with the beta cells in the islets of Langerhans responsible for the production of insulin. A miscalculation in insulin treatments can lead to excess levels of insulin in the bloodstream which can result in a sudden drop in blood glucose levels – hypoglycemia.
If there is no insulin at all, insulin injections have to be given. This is commonly seen in patients with diabetes type 1.
It indicates an abnormally high level of blood glucose. The causes include disorders of glucose metabolism. It can also occur during the administration of insulin injections to battle diabetes. High insulin levels are also seen in conditions such as metabolic syndrome where insulin level is unusually high but ineffective.
“Hyperinsulinemia in the basal state of any origin produces widespread insulin resistance. All tissues that have insulin receptor pathways will be affected, including the pancreatic β-cell, and possibly the brain. Defective insulin signaling at the β-cell impairs glucose-stimulated insulin release. At steady state, basal hyperinsulinemia generates and sustains insulin resistance, irrespective of where the pathology started. Hyperinsulinemia, insulin resistance, and impairment of glucose-stimulated insulin release are intertwined biologically. A single process (hyperinsulinemia) could generate all three simultaneously.”7
This occurs when the insulin level is normal or even raised, but for some reason it is not effective in the metabolism of glucose, the cells of the body become “resistant” to the effects of insulin. This leads to uncontrolled high blood glucose despite the relatively high circulating insulin. This is one of the causes of diabetes type 2 and a common sign in metabolic syndrome.
“Resistance to the biological effects of insulin is a hallmark feature of the MS (metabolic syndrome) and an important contributing factor in the pathogenesis of T2D (type 2 diabetes). In the early stages of insulin resistance, the pancreas compensates by increasing the secretion of insulin into the bloodstream in an attempt to overcome defects in peripheral insulin action. In response to this increased demand for insulin production, the β-cells hypertrophy. Under fasting conditions, basal compensation is sufficient to maintain blood glucose in the normal range. Following a meal though, when glucose is rapidly absorbed from the gut, a relative lack of insulin due to inadequate compensation is detected as the glucose excursion over time is exaggerated. This inability to take up and dispose of glucose appropriately following a meal or glucose challenge is known as glucose intolerance.”8
(1, 3) Glucose Metabolism and Regulation: Beyond Insulin and Glucagon. Aronoff, S.L., Berkowitz, K., Shreiner, B. & Want, L. Diabetes Spectrum. 2004. http://spectrum.diabetesjournals.org/content/17/3/183.full
(2) Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes. Fu, Z., Gilbert, E.R.& Liu, D. Current Diabetes Reviews. 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934755/
(4, 5, 6) Glucagon secretion from pancreatic α-cells. Briant, L., Salehi, A., Vergari, E., Zhang, Q. & Rorsman, P. Upsala Journal of Medical Sciences. 2016. https://www.tandfonline.com/doi/full/10.3109/03009734.2016.1156789
(7) Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training. Roberts, C.K., Hevener, A.L. & and Barnard, R.J. Comprehensive Physiology. 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129661/
(8) Insulin Resistance and Hyperinsulinemia: Is hyperinsulinemia the cart or the horse?. Shanik, M.H., Xu, Y., Škrha, J., Dankner, R., Zick, Y. & Roth, J. Diabetes Care. 2008. http://care.diabetesjournals.org/content/31/Supplement_2/S262.full