Normal Glucose Metabolism in Carnivores Overlaps with Diabetes Pathology in Non-Carnivores

Abstract

Carnivores, such as the dolphin and the domestic cat, have numerous adaptations that befit consumption of diets with high protein and fat content, with little carbohydrate content. Consequently, nutrient metabolism in carnivorous species differs substantially from that of non-carnivores. Important metabolic pathways known to differ between carnivores and non-carnivores are implicated in the development of diabetes and insulin resistance in non-carnivores: (1) the hepatic glucokinase (GCK) pathway is absent in healthy carnivores yet GCK deficiency may result in diabetes in rodents and humans, (2) healthy dolphins and cats are prone to periods of fasting hyperglycemia and exhibit insulin resistance, both of which are risk factors for diabetes in non-carnivores. Similarly, carnivores develop naturally occurring diseases such as hemochromatosis, fatty liver, obesity, and diabetes that have strong parallels with the same disorders in humans. Understanding how evolution, environment, diet, and domestication may play a role with nutrient metabolism in the dolphin and cat may also be relevant to human diabetes.

Hepatic fatty acid biosynthesis is more responsive to protein than carbohydrate in rainbow trout during acute stimulations

“…Notably, similar demonstrations were reported in cat and mink (68,88), showing that fatty acids are not synthesized from glucose, probably due to the absence of glucokinase in feline liver (48,71). The results also confirmed the presumption of Hemre et al (31) that carbohydrate is needed to stimulate lipid biosynthesis, not so much through delivery of carbon backbones, but rather via increased availability of cytosolic reducing equivalents and are consistent with some other demonstrations in carnivorous fish (4,20,26,84).…”

Comparison of carnivore, omnivore, and herbivore mammalian genomes with a new leopard assembly

“…Although carnivores derive their energy and nutrient requirements primarily from animal tissues, they also require regulatory mechanisms to ensure an adequate supply of glucose to tissues, such as the brain [34]. The glucokinase (GCK) enzyme is responsible for regulating the uptake and storage of dietary glucose by acting as a glucose sensor [35].…”

Amino Acids Attenuate Insulin Action on Gluconeogenesis and Promote Fatty Acid Biosynthesis via mTORC1 Signaling Pathway in trout Hepatocytes

“…Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry [23,46]. Presumably, ingested protein/AAs not only regulate protein metabolism, but also modulate glucose and lipid metabolism.…”

“…Rainbow trout, like domestic cat and dolphin, exhibits relatively high dietary protein/ AAs requirement, poor utilization of dietary carbohydrates and glucose intolerant phenotype, thus it represents a relevant carnivorous model organism for the investigation of protein and glucose metabolism [23,24]. Furthermore, given that healthy carnivores exhibit metabolic changes after fasting or a carbohydrate rich diet that are similar to those observed in humans with diabetes, trout can be used as a comparative natural model for the study of common pathologies associated with type 2 diabetes [23].…”

“…Furthermore, given that healthy carnivores exhibit metabolic changes after fasting or a carbohydrate rich diet that are similar to those observed in humans with diabetes, trout can be used as a comparative natural model for the study of common pathologies associated with type 2 diabetes [23]. Therefore, understanding how nutrients regulate intermediary metabolism in trout may have dual significance.…”