[ Diabetes Type 1 ]

A New Role for Pancreatic Insulin in the Male Reproductive Axis

The present descriptive study was designed to show comparison of seminal free L-carnitine and sperm quality. We report here that lipin1, a candidate gene for lipodystrophy and obesity that is a phosphatidic acid phosphatase critical in regulation of cellular levels of diacylglycerol and triacylglycerol and a key regulator of lipid utilization, is rapidly and robustly down-regulated in the uterus by estradiol via the estrogen receptor. “As the problems of diabetes increase, it damages the nerves of the reproductive system. You spend 90 percent of your time in the Division of Reproductive Endocrinology and Infertility. “Fifteen per cent of couples have difficulty having babies at all, or are struggling to conceive for a second time. Multivariate analysis showed that pregnant women with a history of fertility problems had a statistically significantly higher risk of GDM than pregnant women without fertility problems. In men diabetes results in erectile dysfunction and retrograde ejaculation.

Kids didn’t happen, it didn’t matter how much I wanted them. It is not well understood whether hyperglycemia or abnormal insulin signaling is responsible, and what stage(s) of spermatogenesis is affected. In most regimens, blood glucose levels were stable throughout treatment. Smokers were excluded to avoid any interference in the findings. There was no family history of diabetes in any first- or second-degree relatives. After informed consent, thyroid profile (serum TSH, T3, T4) of all subjects was done at their first visit. Eventually we become resistant to all this insulin in our blood, just as we would become resistant to a drug, and your body needs more and more of it to do the same job it once did with far less.

The resulting misfolded protein product causes endoplasmic reticulum (ER) stress, leading to pancreatic β-cell death (6). Akita mice develop hyperglycemia, although the age at onset and severity of hyperglycemia depends on the sex, strain background, and whether the mice are heterozygous or homozygous for the mutant Ins2 allele (M.R.L., personal observations; Schoeller et al. [2]). Alternatively, the association may represent shared aetiologies between these events, indicating common risk factors or similar underlying pathologies. Although this effect is usually temporary, it is better to avoid hot tubs and steam baths. Thus, if Ins2 is expressed in the mouse testis, it is very likely that the human testis expresses insulin as well. Diagnosing PCOS Diagnosing PCOS involves several steps.

After repeated disappointment, we decided to take a break and reassess our journey. This case was published in 1987 in “A Nutritionist’s Guide to the Clinical Use of Vitamin B1”. In this study (2), they used males that were either heterozygous or homozygous for the Akita allele; heterozygous Akita males develop hyperglycemia (>300 mg/dL) by 5 weeks of age, whereas homozygous Akita males develop hyperglycemia by 3 weeks of age (i.e., prior to puberty) and die by 8–12 weeks of age unless treated with insulin. There is no dumping or vitamin deficiency in contrast to bypass procedures. RT-PCR demonstrated that, unlike the pancreas in which both Ins1 and Ins2 are transcribed, only Ins2 was transcribed in the testis. Immunolocalization showed that insulin was detected predominantly in Sertoli cells. Persistent vomiting or pain in the upper abdomen should be brought to our attention.

A few experts think you may have an additional half day to one day window of fertility after you first notice the temperature rise, but most say at that point it is too late to create a baby. Although treatment of the homozygous Akita males with exogenous insulin using subcutaneous insulin implants restored spermatogenesis and fertility, this was not due to restoration of insulin within the testes because insulin did not cross the blood-testis barrier. There could be effects on Leydig cells, which contain insulin receptors and are located outside the blood-testis barrier (9). Therefore, they would presumably not be responsive to insulin produced by Sertoli cells. However, because circulating levels of luteinizing hormone and testosterone, which were significantly reduced in Akita homozygotes, were restored by insulin treatment, the primary effects of exogenous insulin appear to be on the hypothalamic-pituitary axis. This study by Schoeller et al. (2) is of clinical relevance to men with type 1 diabetes because it demonstrates that pancreatic insulin is crucial for the male reproductive axis.

The infertility in homozygous Akita males appears to be due to insulin deficiency, not hyperglycemia. It takes the ability to be self critical without giving in to self loathing. On the other hand, it is possible that severe hyperglycemia before puberty interferes with the function of the hypothalamic-pituitary-testicular axis, whereas hyperglycemia occurring during or after puberty only interferes with the function of the reproductive axis after several months of chronic exposure. However, the ability to restore fertility in homozygous Akita males with exogenous insulin suggests that if prepubescent hyperglycemia interferes with the function of the reproductive axis, it is not irreversible. This article (2) opens the door to future studies that aim to understand how insulin regulates the male reproductive axis, and whether insulin is regulating the pituitary, the hypothalamus, or higher central nervous system nuclei. Knockout of the insulin receptor gene in the central nervous system impairs luteinizing hormone production and spermatogenesis (10). There was no significant difference in follicle-stimulating hormone levels between wild-type, heterozygous, and homozygous Akita males, suggesting that the effects of insulin are on the hypothalamus or on the responsiveness of the pituitary gonadotropes to the hypothalamic gonadotropin–releasing hormone.

It should be noted that insulin has long been recognized to play a role in the ovary. Insulin is detectable in ovarian follicular fluid and synergizes with gonadotropins for oogenesis, ovulation, and luteinization (11,12). Because the ovarian follicle is permeable to circulating hormones, it has been thought that follicular fluid insulin is derived from the pancreas. However, in light of this current study, whether insulin (and Ins2 in particular) is expressed by ovarian cells ought to be examined. Although this study did not find an essential role for testicular insulin, additional experimentation, perhaps with testis-specific Ins1 or Ins2 knockout or transgenic strains, is necessary to further understand the function of testis-derived insulin. It will also be important to study the effects of insulin and insulin deficiency that are conserved, as well as those that are distinct, between the hypothalamic-pituitary-gonadal axes of females and males.

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